2. The Vulture
Another brilliant scientist, Adrian Toomes was completely screwed by his business partner who embezzled the funds that were financing his inventions. Taking his last innovation, a flying harness and wings, and using it for a life of crime, the Vulture has been one of Spidey's most bitter enemies.
Hollywood's Pick: John Malkovich
It was rumored back during the dark days of Sam Raimi's Spider-Man 4 that he wanted Malkovich as his main villain. Malkovich also seemed right for the role due to his extensive stints as homicidal masterminds and eccentric crooks.
My Pick: Michael Imperioli
This might sound strange to cast Christopher from "The Sopranos" as the flying, bald, super genius. But stay with me... Imperioli has aged quite a bit since his days in the HBO mafia, and he would lend a certain streetwise crimelord vibe to the character, especially if he's established as being one of the first of Spidey's villains. Additionally, Imperioli has a physicality that would lend well to the flight capabilities and predatory sneers the role demands.