Classic Battle Royale

Mephisto I'll give you that Mephisto does kind of ruin the list but he is absolutely a Spider-Man villain. One More Day/Brand New Day is not their only interaction and while he saved Aunt May, he split up Peter and MJ which was his ultimate goal. This is because Mephisto looked into his own future and saw that he would eventually establish his vanquished kingdom on Earth, only to be defeated by Spider-Man or his daughter (with MJ). Because of this, Mephisto was tormented with the possibility of his downfall and began plotting to ensure that this never happened. Hence keeping Peter and MJ apart as one of his main goals. When they started getting back together, Mephisto was behind the creation of Kindred, giving the Stacy Twins, Gabriel and Sarah, their power with the goal to again come between Peter and MJ. When Doctor Strange figured this out, he confronted Mephisto and asked him what his fixation with Spider-Man was about. Those are just a couple of examples but Mephisto has been torturing Spider-Man off and on for a long time now and they have even battled straight up at least a few times too, with Spider-Man usually needing some help from other heroes, of course. And when talking to Blackheart, Mephisto even told him how he wanted to torture all Spider-Men as he was tormenting Miles Morales at the time. He HATES Spider-Man! Currently, Spider-Man still seems to be unaware that Mephisto is behind a number of his misfortunes, however.

Mephisto @Tyrannus Doctor Doom too