Well, I think the Buddy Cop Genre is only going to thrive based on the two cops in particular. That's what made the Lethal Weapon series as good as it was. It was really never about the Villain. On the flipside, if you have a weak pair of Cops, then the Villain becomes paramount and as you said, it's one and done because no one would really want to come back for the Cops if the Villain was the star.

As for Ruffalo / Downey, that would actually be something fun to write. I may take a crack at it just for personal reasons and if I came up with a story that I liked, I would definitely have an eye on drawing a comic of it.