Day 1 Istanbul, Turkey

The only city in the world that can lay claim to straddling two continents, Istanbul—once known as Constantinople, capital of the Byzantine and then the Ottoman Empire—has for centuries been a bustling metropolis with one foot in Europe and the other in Asia. Istanbul embraces this enviable position with both a certain chaos and inventiveness, ever evolving as one of the world's most cosmopolitan crossroads. It's often said that Istanbul is the meeting point of East and West, but visitors to this city built over the former capital of two great empires are likely to be just as impressed by the juxtaposition of old and new. Office towers creep up behind historic palaces, women in chic designer outfits pass others wearing long skirts and head coverings, peddlers' pushcarts vie with battered old Fiats and shiny BMWs for dominance of the noisy, narrow streets, and the Grand Bazaar competes with modern shopping malls. At dawn, when the muezzin's call to prayer resounds from ancient minarets, there are inevitably a few hearty revelers still making their way home from nightclubs and bars. Most visitors to this sprawling city of more than 14 million will first set foot in the relatively compact Old City, where the legacy of the Byzantine and Ottoman empires can be seen in monumental works of architecture like the brilliant Aya Sofya and the beautifully proportioned mosques built by the great architect Sinan. Though it would be easy to spend days, if not weeks, exploring the wealth of attractions in the historical peninsula, visitors should make sure also to venture elsewhere in order to experience the vibrancy of contemporary Istanbul. With a lively nightlife propelled by its young population and an exciting arts scene that's increasingly on the international radar—thanks in part to its stint as the European Capital of Culture in 2010—Istanbul is truly a city that never sleeps. It's also a place where visitors will feel welcome: Istanbul may be on the Bosphorus, but at heart it's a Mediterranean city, whose friendly inhabitants are effusively social and eager to share what they love most about it.

Day 2 Kavala, Greece

Day 3 Thessaloníki, Greece

Day 4 Vólos, Greece

Day 5 Kusadasi, Turkey

Whilst the busy resort town of Kusadasi offers much in the way of shopping and dining – not to mention a flourishing beach life scene, the real jewel here is Ephesus and the stunning ruined city that really take centre stage. With only 20% of the classical ruins having been excavated, this archaeological wonder has already gained the status as Europe's most complete classical metropolis. And a metropolis it really is; built in the 10th century BC this UNESCO World Heritage site is nothing short of spectacular. Although regrettably very little remains of the Temple of Artemis (one of the seven wonders of the ancient world), the superb Library of Celsus' façade is practically intact and it is one of life's great joys to attend an evening performance in the illuminated ruins once all the tourists have left. The history of the city is fascinating and multi-layered and it is well worth reading up on this beforehand if a visit is planned. Another point of interest for historians would be the house of the Virgin Mary, located on the romantically named Mount Nightingale and just nine kilometres away from Ephesus proper. Legend has it that Mary (along with St. John) spent her final years here, secluded from the rest of the population, spreading Christianity. An edifying experience, even for non-believers. For the less historical minded amongst you, Kusadasi offers plenty in the way of activities. After a stroll through the town, jump in a taxi to Ladies' Beach (men are allowed), sample a Turkish kebap on one of the many beachfront restaurants and enjoy the clement weather. If you do want to venture further afield, then the crystal clear beaches of Guzelcamli (or the Millipark), the cave of Zeus and the white scalloped natural pools at Pamukkale, known as Cleopatra's pools, are definitely worth a visit.

Day 6 Rhodes, Greece

Early travelers described Rhodes as a town of two parts: a castle or high town (Collachium) and a lower city. Today Rhodes town—sometimes referred to as Ródos town—is still a city of two parts: the Old Town, a UNESCO World Heritage site that incorporates the high town and lower city, and the modern metropolis, or New Town, spreading away from the walls that encircle the Old Town. The narrow streets of the Old Town are for the most part closed to cars and are lined with Orthodox and Catholic churches, Turkish houses (some of which follow the ancient orthogonal plan), and medieval public buildings with exterior staircases and facades elegantly constructed of well-cut limestone from Lindos. Careful reconstruction in recent years has enhanced the harmonious effect.

Day 7 Santorini, Greece

Undoubtedly the most extraordinary island in the Aegean, crescent-shape Santorini remains a mandatory stop on the Cycladic tourist route—even if it's necessary to enjoy the sensational sunsets from Ia, the fascinating excavations, and the dazzling white towns with a million other travelers. Called Kállisti (the "Loveliest") when first settled, the island has now reverted to its subsequent name of Thira, after the 9th-century-BC Dorian colonizer Thiras. The place is better known, however, these days as Santorini, a name derived from its patroness, St. Irene of Thessaloniki, the Byzantine empress who restored icons to Orthodoxy and died in 802. You can fly conveniently to Santorini, but to enjoy a true Santorini rite of passage, opt instead for the boat trip here, which provides a spectacular introduction. After the boat sails between Sikinos and Ios, your deck-side perch approaches two close islands with a passage between them. The bigger one on the left is Santorini, and the smaller on the right is Thirassia. Passing between them, you see the village of Ia adorning Santorini's northernmost cliff like a white geometric beehive. You are in the caldera (volcanic crater), one of the world's truly breathtaking sights: a demilune of cliffs rising 1,100 feet, with the white clusters of the towns of Fira and Ia perched along the top. The bay, once the high center of the island, is 1,300 feet in some places, so deep that when boats dock in Santorini's shabby little port of Athinios, they do not drop anchor. The encircling cliffs are the ancient rim of a still-active volcano, and you are sailing east across its flooded caldera. On your right are the Burnt isles, the White isle, and other volcanic remnants, all lined up as if some outsize display in a geology museum. Hephaestus's subterranean fires smolder still—the volcano erupted in 198 BC, about 735, and there was an earthquake in 1956. Indeed, Santorini and its four neighboring islets are the fragmentary remains of a larger landmass that exploded about 1600 BC: the volcano's core blew sky high, and the sea rushed into the abyss to create the great bay, which measures 10 km by 7 km (6 mi by 4½ mi) and is 1,292 feet deep. The other pieces of the rim, which broke off in later eruptions, are Thirassia, where a few hundred people live, and deserted little Aspronissi ("White isle"). In the center of the bay, black and uninhabited, two cones, the Burnt Isles of Palea Kameni and Nea Kameni, appeared between 1573 and 1925. There has been too much speculation about the identification of Santorini with the mythical Atlantis, mentioned in Egyptian papyri and by Plato (who says it's in the Atlantic), but myths are hard to pin down. This is not true of old arguments about whether tidal waves from Santorini's cataclysmic explosion destroyed Minoan civilization on Crete, 113 km (70 mi) away. The latest carbon-dating evidence, which points to a few years before 1600 BC for the eruption, clearly indicates that the Minoans outlasted the eruption by a couple of hundred years, but most probably in a weakened state. In fact, the island still endures hardships: since antiquity, Santorini has depended on rain collected in cisterns for drinking and irrigating—the well water is often brackish—and the serious shortage is alleviated by the importation of water. However, the volcanic soil also yields riches: small, intense tomatoes with tough skins used for tomato paste (good restaurants here serve them); the famous Santorini fava beans, which have a light, fresh taste; barley; wheat; and white-skin eggplants.

Day 9 Valletta, Malta

Malta's capital, the minicity of Valletta, has ornate palaces and museums protected by massive fortifications of honey-color limestone. Houses along the narrow streets have overhanging wooden balconies for people-watching from indoors. Generations ago they gave housebound women a window on the world of the street. The main entrance to town is through the City Gate (where all bus routes end), which leads onto Triq Repubblika (Republic Street), the spine of the grid-pattern city and the main shopping street. Triq Mercante (Merchant Street) parallels Repubblika to the east and is also good for strolling. From these two streets, cross streets descend toward the water; some are stepped. Valletta's compactness makes it ideal to explore on foot. City Gate and the upper part of Valletta are experiencing vast redevelopment that includes a new Parliament Building and open-air performance venue. The complex, completed mid-2013, has numerous pedestrian detours in place along with building noise and dust. Before setting out along Republic Street, stop at the tourist information office on Merchant Street for maps and brochures.

Day 10 Siracuse, Sicily, Italy

Siracusa, known to English speakers as Syracuse, is a wonder to behold. One of the great ancient capitals of Western civilization, the city was founded in 734 BC by Greek colonists from Corinth and soon grew to rival, and even surpass, Athens in splendor and power. It became the largest, wealthiest city-state in the West and a bulwark of Greek civilization. Although Siracusa lived under tyranny, rulers such as Dionysius filled their courts with Greeks of the highest cultural stature—among them the playwrights Aeschylus and Euripides, and the philosopher Plato. The Athenians, who didn't welcome Siracusa's rise, set out to conquer Sicily, but the natives outsmarted them in what was one of the greatest military campaigns in ancient history (413 BC). The city continued to prosper until it was conquered two centuries later by the Romans.Present-day Siracusa still has some of the finest examples of Baroque art and architecture; dramatic Greek and Roman ruins; and a Duomo that's the stuff of legend—a microcosm of the city's entire history in one building. The modern city also has a wonderful, lively, Baroque old town worthy of extensive exploration, as well as pleasant piazzas, outdoor cafés and bars, and a wide assortment of excellent seafood. There are essentially two areas to explore in Siracusa: the Parco Archeologico (Archaeological Zone), on the mainland; and the island of Ortygia, the ancient city first inhabited by the Greeks, which juts out into the Ionian Sea and is connected to the mainland by two small bridges. Ortygia is becoming increasingly popular with tourists, and is starting to lose its old-fashioned charm in favor of modern boutiques.Siracusa's old nucleus of Ortygia, a compact area, is a pleasure to amble around without getting unduly tired. In contrast, mainland Siracusa is a grid of wider avenues. At the northern end of Corso Gelone, above Viale Paolo Orsi, the orderly grid gives way to the ancient quarter of Neapolis, where the sprawling Parco Archeologico is accessible from Viale Teracati (an extension of Corso Gelone). East of Viale Teracati, about a 10-minute walk from the Parco Archeologico, the district of Tyche holds the archaeological museum and the church and catacombs of San Giovanni, both off Viale Teocrito (drive or take a taxi or city bus from Ortygia). Coming from the train station, it's a 15-minute trudge to Ortygia along Via Francesco Crispi and Corso Umberto. If you're not up for that, take one of the free electric buses leaving every 10 minutes from the bus station around the corner.

Day 11 Salerno, Italy

Salerno is an Italian city located on the Gulf of Salerno. Famous for being home to the first medical university, Salerno is a great destination for anyone looking for gorgeous sea views filled with sunshine and Italian food.

Day 12 Civitavecchia, Italy

Italy's vibrant capital lives in the present, but no other city on earth evokes its past so powerfully. For over 2,500 years, emperors, popes, artists, and common citizens have left their mark here. Archaeological remains from ancient Rome, art-stuffed churches, and the treasures of Vatican City vie for your attention, but Rome is also a wonderful place to practice the Italian-perfected il dolce far niente, the sweet art of idleness. Your most memorable experiences may include sitting at a caffè in the Campo de' Fiori or strolling in a beguiling piazza.