Maybe - JUST MAYBE - they could remake the Hoenn region as the first Generation 6 games? It's not entirely impossible. We don't need to go through all that Aqua vs Magma storyline, and we don't need to have the same starters, characters, facilities etc as exactly as they were previously. The Hoenn region could be based years after the RSE plot, with new player characters. Brendan and May could be later battle-able like Red in post-game.
Some of the gym leaders will still be gym leaders, others could retire - like Wattson who was fairly old in the RSE games. Some of the cities or towns could have undergone changes - like Mt. Chimney exploded or Sootopolis got submerged. Fortree could have prospered into a forest maze.
As for the E4, I guess none of them would need replacing (Drake could still be there as the formidable elder). However, I'm still not sure who should be the Champion. Maybe Wally COULD be the champion. Steven could be the CEO of Devon who travels around the region a lot (and showers you with Devon products everywhere), and Wallace could be the Contest Judge or something (if they ever bring back Contests).
Just my thinking