My suggestions for exploring Thessaloniki (100,000 and still growing) are really just that: suggestions. Unlike Athens, with its Acropolis, Thessaloniki has no one "must-see" sight. In fact, it's the city of Thessaloniki itself that's the "don't miss" attraction.
What I like best about Thessaloniki are the endless opportunities for what I think of as focused wandering -- heading off, perhaps, for the splendid Archaeological Museum and the Museum of Byzantine Culture (conveniently located side-by-side) and being pleasantly surprised when en route I come across a previously unnoticed small Byzantine church, or a restored Turkish bath, or a cluster of shoe shops with stunning window displays of knockoff Manolos and Jimmy Choos.
Wander along Thessaloniki's main drags, such as Aristotelous and Egnatia streets, and you'll suddenly realize you're passing (or just around the corner from) the city's main markets, the ancient agora, the clutch of old-fashioned shops and tavernas in Athonos Square, several small churches and Turkish baths, the Alatza mosque, the city's main church, St. Demetrius -- and too many small cafes to count. Don't miss the jumble of old-fashioned shops and chic cafes in little Athonos Square, just off bustling Egnatia. From Athonos, it's only a few steps to wide squares built around churches and Roman palaces, and to harborside promenades with non-stop cafes filled with Thessalonians non-stop talking and texting on their cell phones (kineta).
To get a view of the whole show, climb (slowly, and not in the midday sun) up to Ano Poli (Upper City), the old Turkish Quarter where many tumble-down wooden houses are being restored as boutique dwellings, with enough cafes thrown in for you to find a place to rest. One warning: While you're meandering, don't completely relax. Thessalonians with motorcycles, like Athenians, regard sidewalks as ideal spots to drive and park. And one helpful piece of information to keep in mind while you explore Thessaloniki: As in most Greek cities, there are almost no visible street numbers, nor do Greeks use street numbers when giving directions. Ask for what you want by name or crossroads, not by any street number. Following are some suggestions on how to get to know Thessaloniki (also known as Salonica).
Thessaloniki Culture -- The next Thessaloniki Biennale (www.thessalonikibiennale.gr) will be held in 2013. If you're in town then, keep an eye out for exhibits. The Macedonian Museum of Contemporary Art, 154 Egnatias (tel. 2310/240-002; www.mmca.org.gr) is usually a good place to pick up a program with the schedule of events.
If You Have 1 Day
The city's two major museums -- the Archaeological Museum and the Museum of Byzantine Culture -- are handily located side by side near the fairgrounds. Decide whether you'd rather start with artifacts from antiquity or images of life in Byzantine Thessaloniki, and be the first one through the door at the museum you choose. After visiting the museums (with a break at the excellent cafe in the Byzantine Museum), stroll back along the harbor past the White Tower to the center of town for lunch. If you feel energetic, hop a bus or take a taxi to the old-fashioned Upper City (known locally both as Ano Poli and Tsinari). Then grab a bite, perhaps at Tsinari's Ouzeri, which has been serving up ouzo and mezedes (snacks) since 1859. Once you're fortified, wander back downhill to the center of today's Thessaloniki. Reminder: Most of the churches you want to see throughout Thessaloniki are open morning and early evening, but closed during the midafternoon siesta period (roughly 2-5pm).
After your own siesta, you might visit some of the Roman monuments and the churches of Ayia Sofia and Ayios Dimitrios in the city center, remembering that plenty of cafes are nearby, as well as the famous sweet shop Terkenlis (www.terkenlis.gr) in Ayia Sofia Square. When you're ready for dinner, head to one of the cheek-by-jowl restaurants in the Ladadika, the restored warehouse district that takes its name from the olives and olive oil once stored here. Another not-to-be-missed dinner choice is the justly famous Thanasis, in the rambling Modiano Market.
Note: This makes for a very full day, and you'll certainly enjoy Thessaloniki a lot more if you have more than a day here. Byzantine churches take time to find, to see, and to enjoy. Many of the frescoes and mosaics are high up on walls, or faded by time (a strong flashlight and binoculars are invaluable).
If You Have 2 Days
If you have more than a day, abbreviate your first day, so you don't feel obligated to see the city in one fell swoop. You might begin your second day with the Upper City and work your way downhill. Start at the impressive but overly-restored Vlatadon Monastery and then head down, stopping at the appealing churches of Osios David, Nikolaos Orphanos, and Profitias Elias. Even if church architecture, mosaics, and frescoes are not your thing, you'll enjoy walking through the narrow streets lined with a mixture of tumble-down and restored two-story wood houses dating from the Turkish period. If you didn't see them on your first day, take in the churches of Ayia Sofia and Ayios Dimitrios when you get back down to the city center, and stroll past the Alatza Imaret and Yeni and Bey Hamami Baths, relics of the city's Turkish past.
Then, for a change of pace, take in the city's markets that blur one into another: the Modiano, the open-air food market on Athonos Square, the Kapani (Vlali), and Bezesteni markets. If you visit all these, you can buy anything from a copper bucket for milking sheep to the sheep itself. Along the way, you can nibble on souvlaki, pastry, or whatever seasonal fruit catches your fancy -- and get a bunch of flowers at the Louloudadika (flower market) in a 16th-century Turkish bath, the Yahudi Haman. If you haven't already seen the Arch of Galerius, the Rotunda, and the Roman agora, try to take them in during an evening volta (stroll), with frequent breaks along the way at some of Thessaloniki's myriad cafes.
If You Have 3 Days or More
Everyone in Thessaloniki seems to be rushing. Take advantage of being on vacation and spend some time strolling, wandering, and browsing through some of the shops and galleries along Egnatia, Tsimiski, Aristotelous, Ayias Sofias, and pedestrianized Dimitriou Gounari streets. In the evening, if you want to see young Thessalonians working at relaxing, take in some of the bars at harborside Aristotelous Square, in and just off Plateia Athonos (between Egnatia and Ermou sts.), or at the famous Mylos complex on Andreou Georgou.
When you've had your fill of city pleasures, you may want to head out of Thessaloniki to see some of the sites associated with Philip and Alexander, such as Vergina, Dion, or Pella. If you'd like to avoid a lot of driving, sign up for one of the efficient day trips that take in these sites.