Using the US/Canada example...and removing for a moment the politics and the customs issues...

From a geographical standpoint...and taking into account current service patterns...it's fun to think about what could work. The OP has already posited a SW hub at MDW...obviously, if that works then so would a UA/AA hub at ORD (again, from a purely geographical standpoint).

DL would be positioned fairly well with a Canada-MSP-Canada hub. I could also see AS picking up some British Columbia-SEA-YYZ traffic, with the minor hitch that they don't currently serve YYZ. But geographically, it would work.

On the flip side, YYZ would work fairly well as a connecting point from the western US to New England. If the price was right, I'm sure many folks in the Pacific Northwest would be willing to connect through YVR to head east. (Not to mention Alaska-YVR-lower 48 connections).

But not much else works, geographically, for US-Canada-US connections, especially given Americans' perception of Canada as the "great white North" (even though a significant chunk of the populated part is south of the 49th Parallel.)