Great food for thought on here.
If I may add a few points:
I agree there is a gap in the market for medium size, mid range type. As already stated the B737-8/900 and A321 just don't cut it weight/range when you get up past the 5hr mark. But I think the reason no one has replaced the 757 directly is because even now boeing will admit the 757 is and always was Too heavy for 70% of its routes. i.e. its weight reflects the capability of the aircraft which few operators used more than 30% of its working life.
My operator is curently slowly rolling over from 75/767 to 738 and on the Egyptian routes (ex UK) the 738 is consitently leaving bags behind to lift the weight out of field limited airports. This is unacceptable but will be the future as the accountants love the 737. Personally, once you are past the LCD screens I think its an achaeic deisgn with no business flying in its current guise.
However - the problem as I see it is to be able to design an airframe that is sufficiently light enough in a structural sense to be able to serve the shorter sectors competitively with the 320/737 whilst retaining the performance of the 75/76/310 for the longer sectors.
I don't believe a single design can serve both markets - not with the commercial pressures of the industry at the moment and the 738s and 320s of this world kicking at its heels. The accountants cannot resist them.
My personal view is somewhat simplistic - refurb the current fleet of 757s strip the ETOPS kit out of the a/c (within reason) and install winglets and new engine cores.
An expesive mod but you'll get the aircraft you need as sadly the market for an All in One aircraft is A:too small and B: likely to neither segment justice.