I just played a game of Marvel Heroes that seemed to go on forever. We had 4 players (2 had never played before), and the scenario was drawn randomly (it was Acts of Vengeance). I don't think that Acts of Vengeance is well suited to this play environment. The game lasts for 5 full game rounds unless someone gives the game to the person sitting to their left.
Our game dragged. 5 action rounds per game round and 5 game rounds in this scenario and 4 players. That's 100 player actions (not counting planning). The game doesn't seem to be able to support that much play time. Repetitive nature of headlines becomes more clear. Also limited ability to hinder leader is clear (couldn't play my Dormammu or Ultron on game leader).
In my opinion, Acts of Vengeance is best suited for 2 players. Then the negatives cited disappear. You have complete control of villains (and can win with your super-villain's master plan). Instead of 100 actions there are only 50 (makes the game a lot quicker).
This highlights the "scaling" issues with Marvel Heroes. There are ten different scenarios in Marvel Heroes, and each scenario seems "best" with a certain number of players.
I group Galactus is Coming, Inferno, and Maximum Carnage together. They do have differences, but victory conditions are the same (after 15 points a special headline appears). They seem to play well with 4 players. 15 victory points seems like a good ending for a 4 player game. The game doesn't drag on too long. Repetition doesn't set in. There is even the Special Headline to keep the game interesting (5 or 6 points can be a huge swing).
Other "15 point" scenarios are Born Again and The Brood. Born again doesn't have any flavour, I'd prefer a special headline. I haven't played the Brood in a 4 player game so I can't really comment. However, the possibility that everyone can lose in The Brood should add a co-op element to the game.
The last quick scenario is The Evolutionary War. It is a race against the clock, and only plays for 3 turns (that's 48 player turns quite close to Acts of Vengeance with 2 players). There is a lot of competition for good headlines because you need to average 5 VP per game round to be one of the winners.
The other timed scenario is Onslaught. This plays for 4 game rounds and winners need 20 points. It seems like it would play too long with 4 players, but with 3 players it has 48 player turns just like Evolutionary war with 4. Another 4 game round scenario is House of M and that is explicitly not for 4 players (X-Men aren't available as a team).
So Onslaught and House of M seem better suited to 3 players. What about the last 4 game round scenario: Marvel Heroes. I haven't played it with 3 players. Marvel Heroes seems to encourage defeating the team's Nemesis. Which would lead to cautious play by the villains (losing a mater plan fight gives the heroes 1/3 of victory).
So by my count there are 5 scenarios suited for 4 players. 1 scenario which is especially good for 2 players (Acts of Vengeance). 1 scenario which I'd never play again (Born Again), and 3 scenarios which seem geared towards 2 or 3 players (depending on taste). I suppose the 5 "4 player" scenarios could be played with 3 players, but then the game seems too short for me. Your mileage may vary. Feel free to let me know your thoughts on scenario scalability in the comments sections.