If you ask a Spider-Man fan well-versed in the Silver Age of comics who the web-slinger's greatest villain is, chances are they're going to say the Green Goblin. After all, Norman Osborn has done some pretty heinous things to Peter Parker over the years.
However, if you ask a fan more familiar with the Bronze Age who Spider-Man's greatest villain is, they're more likely to respond with one simple word: Venom.
Yes, Venom has dabbled in being an anti-hero over the years (something the upcoming Venom solo film will likely delve into), and his (main) alter-ego Eddie Brock is an incredibly tragic character. That said, however, the fact remains that the character's one defining trait over the years has been his sheer, unadulterated hatred for Spider-Man and everything he stands for.
In turn, Venom (Eddie Brock's version or otherwise) has put Spider-Man through some serious Hell over the years, be it directly or indirectly, and across multiple different timelines. In the end, it's no wonder their truces always fall through.