The problem is that Boeing built the 757 with just a tiny bit (10%) too little range. It was built to fly NY-LA, and LA-Hawaii; not NY-London. Only recently, has the addition of winglets to a lot of the existing fleet has it become a viable trans-atlantic aircraft, and really the perfect aircraft to fly from a big hub to a smaller city. JFK-BRU, JFK-BHX or BDL-LHR; things like that. I think a new 757-300, with 757-200WL range would be a big seller
Here's the thing: we're probably only looking at maybe 100-200 planes (where range > 739ER, demand marginal for 788, but you want more capacity than a 73G-ER). Amortize the development costs for a new type, and then compare to the option of an airline of buying a real longhaul plane from Airbus/Boeing with 788 capacity to run on a route where there IS sufficient demand and using an alliance partner or their own metal for the shorthaul hop on the other side of the ocean (JFK-IAD/LHR-BRU, JFK-LHR-BHX, BDL-IAD-LHR).
I also tend to think that secondary markets of the type you mention will do pretty well with the 788 if there's really sufficient demand on the route. Take SEA, for instance: very clearly a secondary market on the West Coast compared to YVR, SFO and LAX, but they're well served internationally (LHR, FRA, CDG, AMS, PEK, NRT, KIX, ICN, TPE), without any 757 service outside of FI- in fact, they're in a sweet spot for 763 service (you can hit Northern Europe AND Tokyo with a DL 763 from the Pacific Northwest, and DL does just that in PDX), and most carriers are using A330s and/or 763s (with the occasional 777 and 747).