I like momondo.com because when you search, it has a bar chart of fares by date so it's pretty easy to click on the shortest bar and switch the search to cheaper dates. Also, it groups results by cheapest, quickest and best, which I like. When I was booking flights for our trip later this summer, I started at momondo and then went to the individual airline sites to fine tune the search and actually book the one that had the best route at the best price.
I've also found that on some routes I can save a nice amount by getting myself to a hub airport and flying from there. For example, round-trip SAN to ARN this summer is $979 and you have to go through EWR (an airport I detest), but SFO to ARN via AMS on the same days is only $432.50. It happens that we have enough miles on Southwest to get to SF for free the day before and a place to stay with family that night, but even if we didn't, we could certainly do it for a fraction of the $1093 we're saving on two tickets.
I think the best thing you can do is just do a lot of searches from any airports you're willing to fly from/to, set fare alerts through Google or Kayak and buy when you think they've gone as low as they're going to.