I've booked over a dozen flights online in the last year and a half. I routinely check Orbitz, Priceline, Expedia, Yahoo (since Yahoo has been using Travelocity, I don't bother checking both) and the four airlines with which I have frequent flier accounts. I also used to check 2 different travel agents for each trip. There is no site that consistently offers the best fares or service. I have bought tickets from Priceline, Yahoo, Expedia and Travelocity. The airline sites have been consistently worst unless I'm booking award travel.
Booking air travel is a nasty game that I am far from mastering. Reserving for an international trip last year, I watched the price come down every week (though it was up some days, down some) for over a month until three weeks before my travel dates. Prices started at over $1200 and went as low as about $750 before climbing back to $870 the next day before I jumped on. For the last three weeks, I checked just out of habit and the price continued to rise to over $1300.
You can check four different sites five times each today and easily get 20 different prices. If you care a lot about price, you need a lot of time, patience and a fast internet connection. For service, Yahoo and Expedia are probably the easiest to use, allow you the most options and are good about informing you of flight changes.
Blessed are the cheesemakers.