THere's the obligatory touristy stuff,
see the castle - can do it in 1 day but 2 days slowly is probably better
walk over charles bridges, do it at night, with some mulled wine
Old town square, markets, astronomical clocks and tourists everywhere
See the dancing house
Go to the kafka museum its not bad
DRINK THE BEER! its awesome, also, try wine and coke, mixed.
If nightlife is your thing, theres a club/ bar called cross about 2 blocks north east of Nadrazi holesovice which is cool, its like a junkyard except with seats and indoors, play metal and or reggae.