Spider-Man had already fought and thwarted the Chameleon, the Vulture and the Sandman. He’d nearly been beaten by two doctors named Octopus and Doom. He’d fretted about the frailty of Aunt May and fumed about the unfairness of J. Jonah Jameson. But in Amazing Spider-Man 6 (Nov. 1963), the odds against him were stacked even higher.
Now, he had to defeat Dr. Curt Conners, a man who had accidentally transformed himself into the monstrous Lizard while attempting to restore his lost arm. Like the Hulk, Conners could not control his condition, and he had a wife and small son who loved him. So Spidey had to defeat the Lizard and his reptile army while finding a way to avoid hurting a husband and father. His task was heroic indeed, and this Stan Lee/Steve Ditko story set the pattern for Spider-Man movie villains, who always have a sympathetic, damaged and human side to their dangerous rage.
Also, as Don Alsafi noted, “Finally, it’s impressive to see the continued and steady evolution of Peter's character. As mentioned above, early on in the story he’s about to ask out Betty Brant when he's interrupted by another of Jameson's outbursts, and the story ends with Peter phoning up Liz Allan for a date instead. She turns him down — suddenly enamored with that hero Spider-Man who saved her at the museum — but instead of feeling rejected, Peter just shrugs in bemusement at his wry luck. It’s a significant change to see him displaying this kind of cool confidence, something he clearly lacked in his earlier stories.”