I've read a few story arcs of Captain America, so I know some villains like Baron Zemo, plus I go on Marvel Wiki a lot, so I know Black Panther, Enchantress, and the Skrull. I've also played a few video games based in the marvel universe, so I've seen Ms Marvel and Grim Reaper. I don't read many of the comics, but I do know a bunch of the characters and their backstories. I've seen only a few episodes, though. There are probably a bunch of main villains I've missed and know a lot about.
The story is interesting concerning some of the character's like Hulk and Cap. I don't remember Banner staying Hulk in the comics (though he did speak and control his powers thanks to Tony Stark and Reed Richards) and Captain America was found before the Avengers started I believe, but this is just me being a comic book geek perfectionist.