Once serving as the capital of the Ottoman and Byzantine Empires, Istanbul today offers impressive architecture, historic sites, dining, shopping, nightlife and exotic atmosphere. Spend time in the Old City to explore renowned places, like the Hagia Sophia, Blue Mosque and Topkapi Palace.

Izmir, curled around a cerulean bay, blends 4,000 years of history with a lively cosmopolitan vibe. Enjoy the Mediterranean waterfront, sampling boyoz, kumru, kokoreç and lokma with strong Turkish coffee. See the Roman agora, the patterned clock tower in Konak Square, and the 500-year-old Kemeralti Bazaar. Visit the archaeological museum and take a cable car for panoramic views of the "Pearl of the Aegean."

Mykonos, steeped in Greek myth, was named after Apollo's grandson, Mykons, and linked to the battle between Zeus and the Gigantes. Today it's one of Greece's most beloved destinations, known for its postcard scenery and lively nightlife. It showcases classic Cycladic architecture, with even new buildings required by law to match the whitewashed, cube-like style. Visit Little Venice, Paraportiani Church, and the Delos archaeological site.

Piraeus is the gateway to Athens, the "Cradle of Western Civilization," famed for its lasting cultural and political influence. Driven by tourism and the 2004 Olympics, Greece has redeveloped many sites. Athens remains a historian's delight, with the Acropolis, Parthenon, Plaka's winding streets, the Temple of Olympian Zeus, the Temple of Athena Nike, and the Archaeological Museum's renowned ancient artifacts.

Heraklion, Crete's capital, offers two must-sees: the Heraklion Archaeological Museum, with Minoan treasures and artifacts spanning 5,500+ years, and the Palace of Knossos, a Minoan center dating to c.2000 BC and linked to the Minotaur's Labyrinth. Enjoy harbor views from the 13th-century fortress and waterfront, then try fish taverns serving Cretan dishes like kaltsounia with raki.

Alexandria, Egypt's second-largest city and chief harbor, was founded by Alexander the Great in 332 BC. Artifacts are still recovered from its bay. Explore the Roman Catacombs of Kom El Shoqafa, Pompey's Pillar, the Roman Theater, and the Citadel of Qaitbay, built on the site of the ancient Pharos Lighthouse, one of the Seven Wonders. Stroll through the 115-acre Montaza Gardens.

Alexandria, Egypt's second-largest city and chief harbor, was founded by Alexander the Great in 332 BC. Artifacts are still recovered from its bay. Explore the Roman Catacombs of Kom El Shoqafa, Pompey's Pillar, the Roman Theater, and the Citadel of Qaitbay, built on the site of the ancient Pharos Lighthouse, one of the Seven Wonders. Stroll through the 115-acre Montaza Gardens.

Malta's capital and major port, Valletta was inscribed as a UNESCO World Heritage Site in 1980. Highlights include the 19th-century Mosta Dome, San Anton Palace Gardens in Attard, Lija and Balzan, and the sea views from Dingli Cliffs. Valletta also makes a good base for day trips to Mdina, with St. John's Baroque Cathedral, and Rabat, once part of Roman Melita, with its archaeological sites.

Messina, Sicily's third-largest city, was a key medieval port for knights heading to the Crusades. Though extensively rebuilt, it still has major landmarks, especially the cathedral with its unusual astronomical clock, the 12th-century Catania Church, and the ornate Teatro Vittorio Emanuele. It's also a starting point for day trips to Mt. Etna's Crateri Silvestri.

As is true of the rest of the Amalfi Coast, this city boasts beautiful vistas, charming open-air cafés and captivating landmarks with historic roots. One example is Duomo di Salerno, an absolute must see for lovers of art, history and architecture. This Italian cathedral showcases an impressive design, powerful frescoes and melodious mosaics spanning the centuries as far back as the 11th century, when it was built by the Normans.

Rome offers endless choices: enjoy street performers at the Spanish Steps, wine and people-watching in colorful Trastevere, or the city's rich history and architecture. St. Peter's Basilica is a full-day visit, with the Sistine Chapel and panoramic views from the dome. Don't miss the Trevi Fountain, the Colosseum, and Aventine Hill, which overlooks the Imperial Palaces ruins and the Circus Maximus.