One of the newer villains on this list, Mister Negative was introduced as part of Spider-Man's sort of reboot Brand New Day and served as one of his main villains for that period.
A new take on the Jekyll and Hyde story, Martin Li is a philanthropist whose touch can cure others. However, when he transforms into his photo-negative alter ego, his power corrupts the souls of others and turns them into his puppets. Mister Negative has used this power to become a ruthless Chinatown ganglord and was even able to temporarily turn Spider-Man into one of his henchmen.
He is also served by his team of elite ninja bodyguards the Inner Demons.