Since this game takes place before 5, I fully expect to see a cameo of either Albert Wesker or Jill.
Also, I am betting that the main antagonist is Ada. She is called the "Bitch in the red dress" after all. Really, only Leon seems to even hold any affection for her. She's an interesting character, but the whole "Mouse and cat" flirting game she plays with Leon is getting boring. I'm hoping to see her real death, with Leon or Chris delivering the blow.