There is no such thing as one site. You can use these others mentioned, most of them are good, but you still won't get coverage of Southwest, JetBlue and a couple others. Best thing is just be prepared to put in an hour, try something like sidestep or bookingbuddy to set the bar and then go to Hotwire and see if they can beat it. Then go to Southwest and JetBlue if they have a route you want and get their best price. Then go to Priceline and offer about 25% under your best price and see what happens. Of course only use priceline if you have flexibility. If the price is over $350 and you are going somewhere Southwest flies, consider buying a free flight voucher. They are transferrable, although the seller has to book your reservation for you. These are easy to obtain on Craigslist, usually a little over $300.
If you did all that, chances are about 99% you got the best deal possible. Good luck.