Hi,
My vote goes to Doctor Octopus, because he was the most developed and interesting villain.
I never understood what made the Green Goblin Spiderman's greatest foe (in the movie series). So what if he learned Spiderman's secret identity? He didn't put it to any good use. He only scared Aunt May and since Raimi didn't pull a "Gwen Stacy" (from the comics), Mary Jane didn't die on the bridge sequence. And Doc Oc DID NOT know Peter was Spiderman, and he still got to kidnap Mary Jane just as well, so what difference does knowing Spiderman's secret ID make? Not much, according to the movie-verse of Spiderman.
The Sandman could have been the movie trilogy's BEST villain, but he was underdeveloped. Still, he seemed near invincible (in all his fights with Spiderman, Spiderman kinda got knocked around quit a bit - and "dark" Spiderman didn't kill Sandman by drowning him, so Sandman was basically invincible)