Actually we have to have one more game to finish things up based on some things with Virgil's past. There's just too many unanswered questions left.
The way I would do it is this. First, delve into Virgil's past about whoever the girl was. We'd start the game AS Virgil. Second, we see him go on a trip to insanity land which makes him lust for power and we see that girl die right before our eyes (explaining the line he says in 3 to Dante about strength and protecting). It would be a memory and then Virgil would start lusting for power again. Third, we then play as Dante, who talks sense into him (as they fight, naturally) and Virgil finally comes to terms with what power really is. The ability to do what you can with the tools you already have or even none at all. Overcoming any and all odds even without yamato. Would be interesting to have him fight Dante hand to hand (maybe even with Dante having the sword) and winning. MGS style.
We'd probably need a boss in the next game who confronts Virgil about his past. Some sort of "memory demon". Hell, it could even be Nero asking questions. Some Darth Vader/Luke Skywalker thing. We could play as Virgil first, then Dante, then fight against Virgil as Dante (who's desperate for power to protect people), killing the "boss demon", then fighting Virgil one last time for funsies after he's been talked sense into. Maybe with a splash of Nero here and there. It's kind of like what happens in Dragon Ball Z with Goku, Gohan and Vagita (and Virgil is totally like Vagita. With Dante as Goku and Nero as Gohan).
I swear they got a lot of ideas from DBZ. They made it work quite well though.