You need to go to several different sites to price it out and then see who offers the lowest rates. This will be the best way to find out.
All the online discounters are all pretty safe to go through. Just be sure you understand policies, etc. in case you need to cancel or change your flight. Look over what you book several times to make sure it is what you want/need. As far as the one site that is the best, it's really hard to tell you. They will all vary and change all the time. One site may be lower for one person, higher for the next. You just have to do your research and see what yo find. In my expereince, the cheapest way to go is directly through the airline. In my past dozen trips, that I can remember, the airline has always been cheaper than the online discounters. Just look around and see what you can find.
Check around online. There are several online discounters, like expedia, priceline, orbitz, etc. This is usually the cheapest way to go. But you should also check directly through airline sites to see if they are running a special. It is also easier to make changes if you use the airline directly instead of a discounter. For example, air tran often offers discounted tickets on Tuesdays and Thursdays and it is cheaper than through other online sites. I prefer to go with the air sites directly. Not only are they usually a less than discounters (Sites like Expedia, Orbitz, AAA, etc. charge service fees that can be small and in some cases $50 a ticket), but if you have to make a change or cancel, it is a lot easier than going with the discounters. Also watch in the newspapers and such, they often advertise specials in the newspaper .
Hope this helps!