It seems that Mysterio is gaining some steam, which I think is good. He has to potential to be a really awesome villain, and a threat to Spider-Man in a way that no other villain in the series has been. If you can somehow tie in his story organically with another, lesser villain, that would make for one kick-ass movie, in my opinion.
Lizard should still be paired with Kraven, because that three-way dynamic also poses a totally new and interesting challenge.
To me, the most natural pairing seems to be Mysterio/Scorpion. They would tie in thematically, in that JJJ would try to sell Scorpion to the public as a real superhero, while making Spider-Man look like a villain. Lots of fun truth/reality/illusion stuff. Maybe have Mysterio play mind-games with Spider-Man, JJJ, Scorpion, the citizens of New York, and turn them against one another at will. Maybe Mysterio is the one who manipulates Scorpion into thinking JJJ is the enemy? AND uses him as the brute force he lacks against Spider-Man? These are all just ideas, but I think that's the route to go if you want to make Scorpion more than just a physical threat/Poor Man's Doc Ock.