Well Spider-man has plenty of bad guys. If I had to create one how about.. A bad guy who can shoot bug spray? Named the vile exterminator? Well the name might need work. hehe
The villain known as D'spare did that in an issue where Ben Reilly and Peter teamed up with Black cat.
I would have a villain who is a sort of hero hunter or villain. A little bit like Kraven the Hunter except this guy is slightly more powerful and has actually killed heroes in the past............
How about (and this isn't exactly my own villain, but...) how about a spectral form of the original Kraven? Who is "one with the jungle" or something like that?
Is Mysterio still dead, by the way? Normally it would be hard to cop out cancer but it's Mysterio so the writers can make up whatever.
As for a totally new hero-hunter, we could start the arc by killing off someone powerful who no one cares about (will o' the wisp, maybe?) and having him go after all Spidey's allies first--the Prowler, Black Cat, maybe even Human Torch. His name would be something like "Equilibrium" (there's no way that's not already taken but nothing comes to mind) and he'd be obsessed with ridding the world of supers to create harmony in the world or something. I don't know.