A lot would be the first answer.
Open cities is one thing. There were mods for it for Oblivion and I think there's one for Skyrim too. Mostly a case of replacing the low res city interior on the main world space with the one from the city world space, replacing transition gates with ones that opened and rerouting certain pathfinding scripts. Not easy or a quick job, but it has been done.
Moving building interiors into the main worldspace is something else though. With all the clutter items in homes, you'd need a serious super computer to even run it at a decent frame rate as the game engine loads the cell you're in as well as several more directly around you.
There are also a number of issues such as path finding, rain and snow falling through roofs and also the fact that building interiors rarely conform to both the shape of and size of the building they are in.
To be honest, I'm not sure the engine would hold up against making all building interiors part oft he main world space.