The Green Goblin: Despite a rather underwhelming debut in Amazing Spider-Man #14 (1963), the Green Goblin was still the most mysterious and intriguing figure in Spidey's burgeoning rogues gallery. Unlike other comic book villains, the true identity of the Green Goblin was kept secret from even the reader for several years. According to comic book legend, co-creator Steve Ditko wanted the Goblin to remain completely anonymous, having grown tired of stories where the villain is unmasked as someone known by the hero. Well, thankfully (in this case) Ditko was overuled by Stan Lee, because in Spider-Man #39 (1966) the Goblin was revealed to be Norman Osborn, the father of Peter Parker's best friend. That same issue, Osborn discovered Parker was actually Spider-Man, escalating their conflict to an intensely personal level. Another fascinating (and somewhat groundbreaking) aspect of Osborn was his struggle with mental illness. Sure, insanity had been a pillar of supervillainy for quite awhile, but Osborn's psychosis gave readers a glimpse into the twilight world of mental illness that no comic book had really explored before. This cyclical struggle culminated in the death of Parker's girlfriend Gwen Stacy in Spider-Man #121 (1973), followed by the ironic death of Osborn the very next issue.
Sadly, anyone familiar with the current Marvel Universe knows that Norman Osborn was retroactively resurrected some years ago, was revealed to have secretly fathered two children with Gwen Stacy (!), and is now some kind of out-of-control Homeland Security official bent on world domination. Or something.
Well, in my mind, Norman Osborn is still dead from a bat-glider to the chest...with his evil still haunting Peter Parker from beyond the grave.
Galactus: For the first quarter century of superhero comics, villains didn't do much more than steal money from banks or priceless artifacts from museums. However, in Fantastic Four #48 (1966), Jack Kirby and Stan Lee upped the ante to the Nth degree with Galactus, an elaborately-armored space god so powerful, he could steal the life force of entire planets! Although many near-omnipotent figures have come along since Galactus, ol' bucket-head remains my favorite (despite some funky costume issues in his first few appearances). As the years went by, Galactus became a more ambiguous figure...less a straight-up villain and more a universal force of nature who occasionally assisted the planet Earth when he wasn't threatening to consume it.