One use-case I often have, fwiw, is "what's the cheapest transatlantic flight right now?", which I have to find through trial-and-error. Once I know that, I can often find a cheap way to get to/from the relevant endpoints which doesn't show up on a regular fare search (train, bus, low-cost airline, etc.).
Of course a full end-to-end search that took into account all travel modalities and included all the low-cost carriers would be even better, but that seems like a more difficult information-aggregation problem.
Kayak Explore is pretty good for that. Select your city in the US, then check non-stop and Europe. It's on a map and I would prefer a list, but it does the job. Belfast and Copenhagen are the cheapest transatlantic in March, for instance.
Of course a full end-to-end search that took into account all travel modalities and included all the low-cost carriers would be even better, but that seems like a more difficult information-aggregation problem.