I was thinking about how they could handle Nemesis since REmake2. Since Nemesis is supposed to feel more like a constant threat than Mr.X they'll probably make the city portion of the game bigger and more open with significantly less or no safe areas from Nemesis. Lots of alleyways and streets, specific buildings you can go into and out of leading to other areas of the city, and then just have Nemesis roaming the same map with some of the same triggers that Mr.X had to force confrontations (blowing up the wall in the police station, getting into the room with the jack) and give him access to almost all of the same areas you have. The way I see it going is probably one main big city area with lots of twisting tight streets leading into each other and more of a focus on character movement and dodging.
If they made it more open as well they could retain the random and "random" elements from the original, lets say at the very beginning you have three alleways that all lead to the same area eventually but depending which one you go through will augment the way Nemesis will behave when you get to the next area, where eventually the next augment trigger come in. Defeating him in areas could also still net you bonus weapon parts, but increases the difficulty on him as well afterwords as well as everything you lost to do it.
3 was a different game that had a lot of little quirks and it would be nice to see them acknowledge that and be able to incorporate everything they can from it.
If they turn Mercenaries into Ghost Survivor scenarios i'm gonna be rattled though.