When we travel we usually book using Orbitz.
The reasons are simple— it works and there's no guesswork. We know the price and where we're staying before we book. Orbitz web site also provides the tools I need to find flights by price or by time. And when I save my time I really save.
Our next choice is Travelocity. Their site has an excellent hotel search feature we really appreciate. Reviews from other travelers are helpful too.
And then there's Priceline. You'll find incredible deals here- but we don't recommend it for newbies.

Another option, especially for bundled vacation
deals is Cheap Tickets.
For the real deal seekers we recommend Hotwire.
Set your preference and name your price.