Hipmunk is always my first stop for flights, but the last few I've booked I've ended up finding better deals elsewhere:

London to Toronto (cheaper with CanadianAffair.com)

Halifax, Canada to JFK (cheaper on US Airways site)

Edmonton, Canada to LGA (cheaper on US Airways site)

They're all at least partly non-US, but I was able to find similar price discrepancies with flights from NYC to SF and Seattle. For example, I am quoted $398 ($441 tax-in) for a flight from LGA to SEA round-trip from Aug 25 to Sept 8. Hipmunk gives me tickets from $398 each way, so I'd be paying twice as much minimum.

In Europe, I've found SkyScanner.net to be generally cheaper because they have more discount airlines (namely Jet2, easyJet, and GermanWings; I avoid RyanAir)