This is weird, because I was thinking about this yesterday. If Capcom decided to attempt an open-world RE game, I personally would prefer it to be set in Racoon City, and story-wise to begin the week the first "cannibal" murders happen, and go right through to the end of RE3. You would be able to create your own character, from their look, to their skills, to their profession.
If you choose as a profession to be an RPD officer, you would investigate the murders, gather evidence, etc. Later, after the outbreak at the Spencer mansion occurs, you would look into the aftermath, and during the Racoon City outbreak, man the barricades, look for and protect survivors, etc.
You could choose to be an Umbrella scientist, working with the virus. Or a doctor at the Racoon City hospital. Your combat skills would be negligible, but you would have a greater understanding of the virus, and be more proficient with healing items.
Over the course of the story, you'd have the opportunity to find evidence of Umbrellas involvement, and depending on the profession you pick at the start, like the RPD officer, for example, you can decide what to do with the evidence, look into it, keep it for blackmail purposes, hand it over to Umbrella, or destroy it.
Which could play into a morality system, like Mass Effect or Fallout.
If multiplayer was included, the best way to do it would be as a separate mode, unlike games like The Division where it's combined, and let those who prefer to go through the story alone have the option.
Of course, the likelihood of Capcom doing any of this is slim at best. They've got a formula, one that works for them, so they won't be giving it up anytime soon.