SideStep.
This site searches over 200 travel booking and airline sites--including Expedia, Travelocity, and JetBlue--and displays results in its downloadable toolbar. When you research a trip on a travel booking site, SideStep's toolbar automatically pops up to show you the itineraries it recommends so you can easily comparison shop. You can search for airfares, hotels, cars, vacation packages, cruises, and more.
Airfarewatchdog.com. The folks at Airfarewatchdog.com claim that "real people" compare airfares on airlines that booking Web sites don't typically include, such as Southwest Airlines. The site also includes smaller airlines, such as Allegiant Air and international carriers, which don't usually share their best fares with the big travel booking sites. The site is no-frills but includes useful features, such as Fare of the Day and Top 50 Fares.
LastMinuteTravel.com. The name pretty much sums it up. This site is designed to help you find the best fares for airlines, hotels, cruises, rental cars, and vacation packages, particularly for those traveling with little advance notice.
Mobissimo. Unlike some travel booking sites, Mobissimo lets you search for international trips as well as domestic U.S. jaunts. The site is limited to airlines, hotels, and rental cars.
Flycheapo.com. This bare-bones site is useful for finding low-cost carriers within Europe.
WhichBudget. Going beyond Flycheapo.com, WhichBudget helps you find low-cost carriers in 124 countries. The site's text-heavy interface will give you flashbacks to the mid-nineties, but it's worth a visit nonetheless.