Depends on your price range.
If you like a bit of luxury, I can recommend the Pyramida. It's at the end of a couple of good tram routes into the centre of things.
if you like cheap and cheerful we stayed in Botel Albatros - you can google it. Ideal location - 10 minute walk to main square. Restaurant was not very nice/fancy. Only used one morning for breakfast, plenty of nice places outside to visit. Room was clean and was an experience being on the river.
Try the Veronsky Dum. It's a small and beautifully restored 16th century town house just 100 yards from Charles' Bridge (on the interesting side of the river, not the commercial one). The staff were very friendly & helpful
and it has a wine bar with the largest list of 'by the glass' wines I've seen. Well worth the money! (they sometimes have extra day free offers) - (just don't tell the whole world or it may get spoiled!)
can second the vote fot Hotel Julien,had good stay there 2006 price /service/ staff /room/food all above average plus intimate classy cellar resturant to get romantic in..we will be useing them again.......