We've just had a long weekend there, and loved it. We walked miles every day just wandering around taking in the city. We planned it in so far as we knew we wanted to visit the Accademia and Uffizi, and we knew that most museums and galleries are closed on Monday so needed to plan around that, but otherwise just played it by ear.
We stayed here, on the recommendation of a friend. Central, comfortable, good breakfast and walking distance to everywhere we wanted to go, and - added bonus - has a roof terrace with great views where you can BYOB for a sundowner.
We didn't pre-book, so did have to queue a bit for the Accademia and Uffizi but nothing too excessive.
We really enjoyed the Duomo museum (we bought a combined ticket for the museum, baptistry, crypt and clock tower). If you do that, worth going to the museum first. The ticket lasts all day so if the queues for the other bits are long you can go off, do something else, and come back later.
We also visited Santa Croce - hadn't planned to but we were wandering around the area and decided to go in - well worth it.
Most of the museums are closed on Mondays, so we walked over to Piazzale Michaelangelo for the views, then visited the Boboli Gardens, and had a long walk along the river.
We got tickets for the opera at the Teatro Maggio Musicale - again very central. It's a modern auditorium with great acoustics.
We didn't have a bad meal all the time we were there, but had a really good dinner at Il Desco and also at Oliveiro (sorry, couldn't find a website for the restaurant itself).
Enjoy!