My initial experiments with Kayak over a year ago left me unimpressed, but Kayak.com has evolved into one of the best tools for finding cheap flights.  There are several notable features that make it a great way to search for flights when you have some flexibility and want a good price:

* You can select a date range of up to 3 days before and after your departure and return.  Without this feature Orbitz was probably better than Kayak for discount flight seekers, but now that Kayak's got it you are able to get a good fare picture for a range of dates.  

You must sign up for this but all that requires is a 10 second email signup.  A huge hat tip to Kayak's team for recognizing that even requiring a name and address is a barrier to sign ups.  Get all that mundane detail from people later or not at all.

* Also great is Kayak's ability to select different arrival airports with immediate fare updates allows you to fine tune your driving to flying ratios.   Especially helpful when traveling to areas where several major airports may be in close proximity to many final destinations.   BWI, IAD, and PHL for example or SFO, SMF, and OAK in California.