Well, as long as they know their limits and do not fly too close to the sun like Icarus, I would say it could be doable.
Anyone played S.T.A.L.K.E.R.? I think that's the type of "open world" they should aim for. The game is open world but not 100%. It has large sections all divided up into "zones". I think RE could achieve something similar to that, especially in a Raccoon City like environment.
Thinking Biohazard 3 maps here, where Raccoon City on the map screen has several locations like "Uptown" and "Downtown" etc.
Instead of just opening and closing doors to progress in each area, every section of the city could be wide open and fully explorable, with handcrafted items all set in place (some items of course would be not accessible until you advance further in the story)
It would have to be done in a way that feels natural though, the last thing we need is a Biohazard game that's big but feels floaty and arcadey with big artificial words popping up telling you where you are every time you enter a new area.
I think also another cool location, if they don't want the game to take place in a city, would be the somewhere in the Kuril Islands. Considering recent events that I do not wish to discuss, I think that would be a really cool location for some kind of outbreak and various factions could be involved (Blue Umbrella, The Connections, The local government forces, etc.), add an open world environment and player choice over which faction to join the possibilities are multitude here.
This is just pure speculation and fanfiction though so please don't anyone start rumors based off of what I am suggesting here xD. I do not work for Capcom but sometimes I think I should.