Expedia is a general-purpose travel website. You will know the hotel and type of room you are booking. Sometimes Expedia will negotiate a good price with a hotel, or offer a discount if you combine the hotel reservation with a flight and/or car. Travelocity, Orbitz, and Hotels.com are similar websites.
Tripadvisor.com is a little different and is worth looking at. It is more of a community-type site that collects travelers' reviews of individual hotels. When you go to check a hotel price on Tripadvisor it will "outsource" the search to one or more websites such as Expedia, and deliver you prices from each site. I like to use Tripadvisor to see what other travelers think about various hotels I'm considering.
Priceline is even more different. It's an auction-type of site that delivers rooms at rates that you select based on hotel class. You can pick the general geographic area (city center; north of the river; etc.) of your hotel and the hotel class, but beyond that you don't know which hotel you're staying at until your offer is accepted by the hotel. You also pay up front with Priceline. I've used Priceline very successfully for rental cars ($15/day in one case) but not for hotels, because I like to know exactly where I'm staying before I make the reservation.