If it's a domestic flight, I usually check southwest.com and then expedia.com too to see what other airlines are offering. All other things being equal because of the great change policy, I pick Southwest. When I find light I want on Expedia (place Southwest doesn't fly and / or better price - time combination that would keep me from doing Southwest) if all flights are all on one airline I book on that airline's website. If they are a mix of airlines I book on Expedia, as I typically can't book this online on an individual airline site, and Expedia works great for this.
I've tried Kayak.com, but really don't like that site. They list flights with layovers that are too short where you could never make your connection and flights with layovers that are ridiculous like 8 hour long, 10 hours long, etc. When looking at them I usually sort results by duration and then skip through lots and look at the ones with reasonable prices. If it's a domestic flight in the continental USA, I don't even look at them. // To Hawaii and to Europe, though, I look at them too on top of Expedia. But be very careful when you look at this one. Also, please note that I don't do a lot of travel to Hawaii or Europe, so don't have much expertise on that front. But I did find the Kayak site helpful to see more options for a trip last summer to Kauai and a trip this summer for my son in a study abroad program.
