I search for flights on Orbitz.com, sometimes take a peek at Expedia (although one must confirm the fare is BOOKABLE, as I've tried to book a really low fare and a "Sorry, this fare is sold out error" message occurs)
Having found the best schedule/airline (if the trip is on one airline), I go to that airline's website and book. 95% of the time, the airline website is the same price and one can get 1000 bonus miles for booking directly (on many airlines). I think AA, US, CO and DL all have lowest fares on home site guarantees.