I'm on the road a lot. For years I used a travel agent but I found out I liked my choices of routes, segments and aircraft better. I am picky about certain things...such as which plane type, which connecting airport, what time do I get in, and a few other seemingly small details that often end up biting you in the ass if you're not careful.
Now, none of the above matters much if all you're looking for is the cheapest fare. Most of my travel is business related and for that I have to buy full fare tickets, just in case my itinerary suddenly changes. In that case, I can still use the tickets without penalty. For best fare numbers, I would use the above detailed search techniques, just tell the web site search engine to search for lowest fare. My sister-in-law swears by Hotwire.com.
I try all the usual sites like Travelocity, Expedia and the others, then I go to the airlines' web sites for more detailed searching since the web travel agents listed here often don't have all the flights available. Quite often, the airlines don't release info about certain flight over the web. I don't know why, but I guess they are trying to steer the flying public to certain flights, segments, and markets.
Anyway, after thoroughly searching my brains out and wasting far too much time...I print out the options I like and call the airline that I have miles to burn with and make a reservation. I then make sure they send me an e-ticket receipt by email or fax.
Good luck!
[beer]