Hey there,
I'm pretty often in PRG and I always book smaller hotels slightly east of Centre / Josefov (Dlouha, Rybna etc). Walking distance (5 to 30 mins) to all major sightseeing items. Not sure about your budget but last Nov I have found a pretty nice place called "Hotel & Apartments Susa-Due" - clean, convenient and a good proximity to the night-life places. Also budget-effective.
mf