Matrix is the engine behind a number of common travel sites (like the aforementioned Orbitz and Kayak, to name just two). So instead of wading through those sites, with their advertising and additional overhead, you can go to Matrix directly.
The site is simple to use, and the search results page offers a slew of convenient ways to sort and filter the results. You can't book through Matrix, though -- it's a search engine only. So when you find the flight you want, just take it to the airline directly.
I especially like the time bars, which lets you display your flight results in a time grid, making it easy to pick the right flight if time is the top priority. [via Lifehacker]