I had a similar thought actually (not surprising as I play DCUO) but wanted to include either AIM or Hydra as the leaders for villain's side. Good MMO gotta have different factions so you can pvp.
Dont forget folks, we're also supposed to introduce a hero as well!
For myself, Im not too sure what I'd do. I'd want this to be a celebration of the MCU. By the end of Infinity Wars we're looking at a dozen years of (presumably) successful films and three different formats brought together (four including the game). And I'd want everyone invited to this party. Coulson, Quake, Mockingbird, maybe even Melinda May or Deathlok (if he's alive? I dont recall). All the Netflix guys, all the (still living) movie guys......get 'em all in! Try to cameo everyone, even that nameless SHIELD agent from Winter Soldier who made it into Age of Ultron.
Well, the Guardians and Agent Carter might have to be DLC. Unless you're dealing with time or space travel, too much work to include. Easier to just drop them in as DLC extras.
Im picturing something like the Elder Scrolls, where you've got a huge map to explore but also enter smaller areas like dungeons (which can still be quite large). I'd want a unit with me; a group of four characters I can switch in and out to fit the needs of whatever I'm doing. Sneaking past the outer defenses of an AIM lab? Take the stealthy and computer literate characters (maybe Quake, Ant-Man, Widow, Spider-Man). Have to break through heavily defended AIM fortifications and reach their computers before their data is erased (time limit!)? You need people who hit fast and hard so maybe Iron Man, Thor, Quake again, and Captain Marvel. Fighting MODOK? Grab Hulk, the Witch, Strange, and Luke Cage.
Maybe give each character a switchable ability tray so they can focus on different skills. Maybe you can switch between Hulk (strong, tough, fast) and Banner (good with science stuff, computers, relatively more sneaky). Maybe Iron Man has his regular, well balanced suit and the Hulkbuster, which would dump speed, ranged options, and utility for melee damage and HP (boss fight!). Maybe Quake can switch to "SHIELD agent/hacktivist" and go all sneaky and computer-y, or go "Inhuman/Secret Warrior" and go crazy with the super powers.
For my new villain and big bad behind it all....the Maestro. After Thanos, not much is going to impress, but I'm willing to bet a grumpy, super intelligent old Hulk from the future wearing the Destroyer as armor, Captain America's shield, and the Eye of Agamotto would do the trick. And I think the semi-big thing I would do is introduce the future of the MCU. We've seen the past in Agent Carter and Captain America, outer space with the GotG and Asgard with Thor. So the Maestro would introduce the MCU to a (completely re-envisioned) 2099. No idea what the plot would be past that. Stuck in the Hell's Kitchen of 2099, pulled there by desperate rebels hoping the heroes of legend can defeat their oppressive overlord, who just so happens to be an Avenger?
No idea who I'd introduce for the new hero. Red Hulk maybe? Get Hurt (or whoever it is who plays Ross) to play the role? She-Hulk? Squirrel Girl? I dunno.