Tom Kenny (whether it be as the voice of Iron Man or Captain America) is the only actor to appear in all fifty-two episodes of the series.
Shawn Ashmore and Ray Stevenson reprise their roles in some episodes. Shawn, who played Bobby Drake/Iceman in the X-Men film franchise, reprised as the voice of the character. While Ray, who played the anti-hero "The Punisher" in Punisher: War Zone (2008), reprised his role as well.
Spider-Man was originally planned to be a reoccurring character in the show, but because Sony Pictures owned the rights, he never made it in, despite Spider-Man having quite a few toys in the line that this show was based on. Despite the embargo, he did appear in material outside of the show, such as games, where he was voiced by Josh Keaton.