The problem lies not with the villains but Marvel's editorial and creative output.

You could easily turn any villain into heavy weight (see Doctor Octopus and Norman Osborn in recent years) but Marvel seems to get more run out of stories where heroes face again other heroes. Which is why other then Infinity, Siege (if you don't count Sentry as a hero during that event) and if you count it the first Annihilation, every major Marvel event story has had some form of heroes fighting against other recognizable heroes or their doppelgangers.

They had a shot with AXIS but you see where they let that one run off to. Best villain show cases maybe individual series but sadly the way Marvel works only a quarter or less of the fans ever get to experience it.