I would argue the Fantastic Four. Even as the team grew in power, their villains sans Doom and maybe the Wizard didn’t get the memo.
In terms of sheer numbers, I'd say the Black Panther. In terms of development, I'd say Iron Man.
Iron Man. I mean I struggle to name many villains that actually originate with him.
In a weird roundabout way, Avengers Infinity War and Endgame kind of brought the Thanos and Stark rivalry back.
Even though he is more an Avengers/FF enemy, I always thought Kang made a good rogue for Iron Man. The self proclaimed futurist vs a literal man from the future. (He also turned Iron Man evil during "the Crossing" and a young version of Kang took inspiration from Tony as part of the Young Avengers.)
"The White Queen welcomes you, TO DIE!"
"We live in a world of cowards. We live in a world full of small minds who are afraid. We are ruled by those who refuse to risk anything of their own. Who guard their over bloated paucities of power with money. With false reasoning. With measured hesitance. With prideful, recalcitrant inaction. With hateful invective. With weapons. F@#K these selfish fools and their prevailing world order." Tony Stark