CheapOair is one a use a lot to find the cheapest airfare. Through this site I was able to get 4 round trip tickets from Vegas to Honduras last minute under $2200. I think that is pretty good!
Travelocity makes it easy to compare airfares. You can also set up fare watchers.
Priceline has been one of my favorite sites for a long time. I have been successful bidding on several occasions and felt like I saved a lot of money.
Flight Network runs some pretty good deals at times. So, they are always worth checking out. You never know when their deal might be to your city.
HipMunk is a newer website that I've been using a lot to check airfare prices. I love the way they display the choices.
Travelzoo has deals on everything involving a vacation: lodging, airfare, activities, and more. I'm always booking something through them.
Hotel Tonight is a new travel app that can save you a load on hotels. They release a list of available hotels at noon each day. If you can tolerate not booking a hotel until the last minute, then this site will save you large amounts of money.