There is one small aircraft/long haul I can think of. BA is planning a 319 service from LCY to JFK.
I've thought for a while that there must be a market for long haul 319/738 ops from regional airports. I'm sure a twice weekly 738 from somewhere like NCL to NY (even if its not JFK) could be made to work. Obviously tickets would be a bit more expensive because of the reasons people have said, but if you could price it at a cost that was comparable to a routing via LHR (+ a premium for convenience) I am sure people would pay it.
However, the fact it hasnt been done suggests to me its just not practical. After all, if money was there to be made, at least one airline would have tried it. And lets be honest, Airline Executives are going to be a bit more clued up than most of us on PPRuNe
RTG!