I have used nearly all of the available services to search for dozens and dozens of flights. All of them had their drawbacks, and no one site seemed to meet all my needs, until I was turned on to www.kayak.com by my geek buddies.
Kayak aggregates all the various other sites and sometimes hooks in directly to airlines. It provides the most comprehensive list of flights, and it has the best user interface available. You can look at a matrix of flights so you can optimize your choice of date, airport, and number of stops/time traveled. When you finally do find a ticket, it is easy to go ahead and buy from the site of choice. It's the Web 2.0 of airplane ticket vendors.
So, enough of all that cheaptickets, travelocity, orbitz, priceline, and all those other garbage sites. Come Kayak with me!
And just in case this sounds too much like a sales pitch, no, I'm not getting paid anything by anybody for this endorsement.