1.Doctor Octopus: Not close to comic book Ock at all, but he works for the context of the story. He's used as a mirror to Peter someone who's making all the same mistakes he is and helps him grow as a person. There's really nothing here that should make us like him anymore than any of the other villains but the way he's used, our subconscious connects him to Peter since he's going through the same arc he is. He sums up the theme of the movie beautifully as well with the line "but it's my dream".
2. Green Goblin: He is Peter's greatest fear realized and a perfect villain for the movie with the message they were trying to send. You do not what's right for you but what's right for others, with great power comes a great responsibility to the world, because the ones you love will always be the ones who pay. Uncle Ben died because Peter was irresponsible and paid for Peters mistake, and once Goblin finds out Peter's identity he is quick to attack those he loves, to make them suffer for him. This is twisted and great.
3. Harry Osborn: Note I say Harry NOT NEW GOBLIN. Harry is a twisted product of Norman Osborn's neglect and a son's desire to make his only parent say he's proud. Through all of the first film Norman speaks to Harry like he's a little boy or an embarrassment, then the last time he speaks to him he tells him just how proud of him he is (unknowing it is because he has given him the key to get to Peter). You can see the pride on his face and the he's finally made his father happy, then the next time he see's him he's dead being laid on his bed. He's a psychotic wreck and he's a perfect example of those suffering for Peter. "...I swear one day Spider-Man will pay...You're all I have left Peter", even though that quote is from the first it sums up his role in the second film brilliantly and why I put him at 3rd.
4. Venom: This is tough he's not done as well as he could be but the way he's used is effective. Spider-Man 3s biggest problems lie in the fact it shifts too far from the original vision of the previous films being, "a story about a girl". In the middle of the film it really doesn't seem like it knows what its doing at all. Regardless by the final act when Venom shows up they have a little bit of a better idea. The theme is trying to be Revenge. Venom is Peter's darkness that he had to let go of, but Eddie is someone who refuses to change and let's revenge consume his life. By jumping into the symbiote he symbolizes that he is clinging onto his hate and his grudges, something that leads to his demise. (I will note I prefer his death in the novelization, being consumed by the symbiote, a better more realistic take on the metaphor than the suicide.)
5. The Lizard: He isn't much more than Peters token adversary, but he isn't made to be much more than that anyway. I guess in away he's what Peter could become, most of his scenes where he has meaningful dialogue with Peter post transformation were cut. Anyway the fact Peter gave him the formula compliments what Uncle Ben and Captain Stacy taught him, that he needs to be responsible and help others, prove he is a hero. He's bellow the others because he could be easily exchangeable, but they didn't do anything bad either so he's above the bellow mistakes.
6. New Goblin:: He is an unfortunate side effect of the film. It seems to me he's like a child conceived in an affair that a husband now has to take care of, an obligation. After the changes were made to Spider-Man 3 Raimi had to drop Vulture but after the cliffhanger at the end of the last film he was stuck with this lose end to tie. It looks to me like he tried to tie it into the whole Revenge theme by making him a personal menace to Peter, rather than a super villain. You will notice he commits no crime besides assault and blackmail and he is never on screen while Peter is fully masked. However he learns his lesson after doing nothing but breaking up Peter and his girlfriend, yet for some reason the plot makes him die...Maybe he's paying for Peter's mistakes but since the movie is a commentary on revenge that doesn't cut it for an explanation. On top of all that he's knocked out of the plot of the majority of the movie because, since they can't get rid of him they need to get him out of the way. Also his origin is extremely rushed and he isn't anywhere near as mad as Norman was. Very very anticlimactic.
7.The Sandman: Probably the biggest contrivance in any of the films, Sandman is Uncle Ben's true killer in an attempt to book end the trilogy. However his character is ruined by the fact he should not be there. Really he has no purpose in final product. I'm sure he did in Raimi's symbioteless script for Spider-Man 3, but he is just out of place here entirely. He's someone for Peter to take revenge on and an attempt to tie together all three films, but this role is also filled by Harry. Harry has a revenge arc has been going on since the end of the first installment and Peter tries to take Revenge on him at some point. Venom symbolizing refusal to give up the grudge and Harry making the decision too late (even though he didn't) were the only roles necessary for the plot. Raimi and Tobey should have just sucked it up and saved him for #4 (which might have been there if Sandman wasn't here).
Anyway the Lizard wasn't bad but thats because he wasn't developed particularly much at all (good or bad). The scenes with his family would have helped and I don't care what you say tampering or not, there were some good lines from the trailers they cut out of the final cut that would have DEFINITELY helped. Plus I could have added Dr.Raffa as I found him to be a very interesting antagonist with a very cold presence. Whatever, just my two-cents on the issue.