www.fly.com claims to search every airline and a range of online travel agents to find the cheapest economy and premium fares, and then lets you refine the results to suit your requirements. You can use sliders to specify your desired take-off and landing times and trip duration, select alternative airports that may cost less to fly from, and view available flights in three different formats: summary, list and matrix.
This customisable approach is far preferable to scrolling through pages of results while the site's minimalist layout is a pleasure to use.