- Multiple-Carrier Searches
You've heard of most of these: Expedia, Orbitz, Travelocity. Many of them return the exact same information; this is because they all use one of four Computer Reservation Systems (CRS). For example, Expedia, Orbitz, Hotwire, and Priceline all use Worldspan.
- Multiple-Carrier Uncertain Searches
A few of these websites offer you discounts if you're willing to sacrifice some amount of certainty (e.g. what carrier, what specific price). Witness Priceline's famous "name your own price" and Hotwire's last-minute deals and "Limited Rates". Lately I've been traveling home for just a weekend, so this isn't worth it (I don't want to fly in late Saturday and out early Sunday!).
- Carrier Websites
Once you have an idea which carriers offer what cheap flights when, it's often actually less expensive to get those flights directly from the carrier. For example, after doing an Orbitz search to figure out what carriers to try, I went on Alaska Airlines' website and found the same flights but without the extra Orbitz charges.
- Budget Carrier Websites
A few budget carriers, such as JetBlue, Southwest, and Virgin America, do not participate in any CRS and thus you have to search them individually.
- Special Deals
Airlines often give special discounts for flying at certain times, etc. Normally you'd have to sign up for their email notification service to get these deals...or you can go to sites like CheapAir, which shows you all the deals if you click "My dates are flexible." Of course, there are lots of blackout dates (e.g. my flight home for Thanksgiving was nearly $400 but if I didn't fly on 11/21 (the day before Thanksgiving) or 11/24-11/26 (the weekend after) then it would be $178 round-trip, even less ($158) flying into Oakland, as long as I booked 14 days in advance.
I recently learned about Kayak, which does a meta-search of various airlines (including the budget ones) and travel reservation sites. While it's probably still worthwhile to check out special deals elsewhere, it could just become my "one stop shop" for airline tickets...
THE BOTTOM LINE: If you're flexible, check out the CheapAir discounts and hotwire last-minute deals. If not, do a Kayak or Orbitz (or whatever other engine you like) search followed up by carrier searches (the ones that came up on Orbitz and the discount airlines).