They could do an iconic antagonist/monster like Nemesis or a Tyrant. Plus, uh, there's plenty more converted "gun" characters in Smash than just Snake (Samus, MM, Fox, Inklings, Mii Gunner, etc, etc). I don't think Chris, Leon, Claire or whoever woukd be a stretch at all.
They won't do a monster. It'd be one of the protagonists, and none of them have fighting styles that could work in Smash without being a really lame copy of Snake.
That's the problem - Wesker is the only human in Smash with potential for an unique moveset, and he's a villain.