I usually book a room via Priceline if I absolutely do not care which hotel I get (only book 4*+) AND I know that I will get a hotel in a particular area of town.
Priceline areas that encompass entire cities (like in Europe) are a no no.
That said, many times you can get very good discount or promo rates on Hilton, Hyatt, Marriott, etc. by booking in advance.