These are villains I think are the most prominent in Spider-Mans crime fighting career, also the most tragic for him to fight. (If they have a more important personal connection to Peter Parker they are closer to 1).
An original member and founder of the Sinister Six, Max Dillon creates hell for Spider-man. Making the wall crawler use Peter Parkers scientific brain to even figure out a way to punch him without getting electrocuted. With a brain scattered from the accident that gave him his powers, Max only wants to get rich and he doesn't care who he hurts in the process. And no he isn't black, like most might think.
An old man, livid about being double crossed by an old business partner, now he's a full time criminal that takes to the skies. Though old, Mr. Tombes is given strength by his suit which also is what gives him the ability to fly. Also an original and founding member of the sinister six.
Another founder and original member of the sinister six. William Baker (Flint Marko) a man with serious anger issues and a pension for violence, became a criminal. Always seemingly being stopped by the wall-crawler, Sandman comes to loath spider-man more than anything. But Peter Parker's scientific mind always seems to figure out a way to inhibit his power.
A special effects expert and master criminal, Quentin turned to crime. Also a founder and original member of the Sinister Six (if you haven't noticed, the sinister six is a big part of spider-man's life). He's even killed spider-man even if it was in an alternate universe. Though you might not know who he is since he hasn't been in a Spider-Man movie (hopefully he will be soon), but he is actually an important villain in spiderman lore.
#6 Carnage (Kletus Kasady)
A psychotic serial killer who once shared a cell with Eddie Brock (see #2), has a taste for killing. When Brock broke out he left some of the symbiote behind (an alien organism that created Venom, Carnage and gave Spiderman his black suit), creating Carnage. Kasady has killed dozens, and put in jail for it over and over again but with the symbiote he is nearly unstoppable. And with a connection to Spider-Man (spiderman, venom and carnage are all connected because of the symbiote), he always seems to know how to hurt him. Oh and he can turn off spidermans spider sense, so he can never see him coming.
#5 Kraven the Hunter
An athlete and gymnast turned famous animal hunter, got tired of hunting animals after having only easy targets remaining in the animal kingdom. So he turned to Spider-Man, for his next trophy. A man so eager for the kill that he even took an experimental drug turning him more animal than man. (Also a founding and original member of the sinister six)
Dr. Kurt Conners was a family man, scientist and also a friend to Peter Parker. Until he took a serum from Lizard DNA, as losing his arm was taking a toll on him. With the serum turning his mind more animal than man, with each dose, Lizard has become one of Spider-Mans most dangerous villains. And spiderman never stops trying to help Conners get better.
#3 Doctor Octopus
Leader of the original Sinister Six. Otto Octavius has four metal arms seared into his spine (apparently changing his mind to accommodate the four extra limbs) and was able to control them like regular limbs, giving him super strength and speed. A genius, he always seems to have a plan to stop spider-man though they never succeed, that is if he can keep his team in line (they are all villains after all).
#2 Venom (Eddie Brock)
Perhaps the strongest villains Spider-Man has to face, since he has his powers. Eddie Brock hated Peter Parker, an expert reporter always taunted Parker. As Spider-Man got rid of his black suit, some adhered itself to Eddie turning him into the opposite of Spider-Man, Venom. Also finding out that Spider-man was Peter Parker made Venom hate both the hero and the secret identity even more.
#1 Green Goblin
The worst and closest villain to Spider-mans life. Once his best friends father, and also murderer of one time girl friend Gwen Stacy by throwing her off the George Washington Bridge. Ever since Stan Lee has created Spider-Man, Green Goblin has been there to terrorize him with his pumpkin bombs.