I see you've mentioned Bucharest in your list, for a weekend city-break. As a travel consultant on Romania, i would advise you to skip Bucharest and go to Brasov (2 and a half hours from Bucharest).
I'm saying this considering you have only 2 nights to stay and that you want something off the beaten path. Bucharest has an incredible nightlife and a charm of its own, but any top city in Transylvania outclasses it.
Brasov highlighs: second most visted city in Romania. The city was built by the Teutonic Knights in 1211 and It's a medieval fairy tale, with The Old Town laying right beneath Mount Tampa. The medieval area is a maze of narrow cobblestone streets and it's packed with fortifications, bastions, gatehouses, medieval inns and bohemian cafes. The Black Church (large Gothic cathedral) and The Council Square are enchanting at any time but especially during winter (a Christmas market is open till mid January).
Very close to Brasov (30 min drive) there's the Bran Castle (Dracula) and Rasnov Fortress (also built by Teutons and settled by Transylvanian Saxons). Brasov even has its own ski resort, called Poiana Brasov.
You have enough time to check out these places during a weekend city break. If you'd like more details and ever consider planning a trip to Romania, i would be happy to help.
I agree about Ghent - amazing city.
I've found another hidden gem recently that's now one of my favourite cities in Europe - Bergamo. I liked it so much as that as soon as I returned from my first trip I booked another flight back! It's an idyllic little place, and has somehow avoided becoming too touristy, probably because everyone overlooks it for Milan (which isn't nearly as nice).
Visit Budapest. It has so much to offer to any kind of travellers.
Just to throw my 2 cent's into the mix:
Tallinn - history, lively, cheap, and stunning
Tartu - if you get away from the town centre you can really feel the older Soviet influence, but it's a student city so quite lively and the campus is gorgeous to walk around (and one of the oldest in Europe!). Also a really interesting art and culture centre in the midst of the older style slat houses
Parnu - lovely beaches, and has a different sort of tourist feel. Is the summer capital (actually pass of their capital, not just an expression of estonia)
Brno - I loved this city. A lot of charm, the Moravian Karst is quite close and you can easily get out for a day of hiking on a day trip from here. There are tunnels under the city, a statue of a man mooning you hanging from the side of a church, and not even remotely overrun by tourists. I thought it was completely underrated.
Warsaw was interesting, but doesn't have the old world charm. I actually found it to be more of a party city than Krakow but that may have been due to where I was staying.
Krakow - I disagree with Andy (sorry, Andy - i know we usually agree, but in this instance...) and found that although touristy, you can easily remove yourself from the party scene and there was so much history and culture there to see that it didn't feel overrun at all. I was there at the height of the tourist season, and liked it so much I rearranged things to spend more time here. and that's excluding visiting Auschwitz.
Bratislava was fantastic - definitely recommend.
Budapest would need at least a long weekend, it will take longer 2 days to get a feel for the city.
I would also consider Zakopane for the high tatras as I've heard great things (I saw them from the other side of the border by taking the train from Poprad up into the ski villages, which is also amazing but may be more difficult to get to on a weekend)
Many places in Spain & Germany can be quite reasonable on a weekend away as well.
Ultimately, my suggestions would vary considerably depending on what exactly you're interested in seeing - are you into history, art, music, nature, etc.? While you can find a bit of each in most cities, the highlights will vary from place to place, and time of year can come into play. I think it would be absolutely lovely to see Tallinn covered in the snow with the markets on, and hiking to the pravčická brána in northern Czech is something that can only be done in the summer.