Luke Cage, Power Mayor (Leadership)

If you want to cut it 40 cards, you could probably afford to lose Hulk, She-Hulk, Valkyrie, Power Man and Iron Fist, and either Squirrel Girl or Hawkeye, depending on the villain and modular encounter(s) you're using.

Righteous Purpose combos with Defensive Formation to keep all of your allies Tough and alive on 1 health (for defending if necessary), so they all have +2 to their stats forever.

This allows Jessica to Thwart for up to 7 pretty consistently, and the otherwise-not-played Fogwell's Gym allows Iron Fist to tank the villain if Luke needs a breather, and then a minion straight after.

Noble Sacrifice can be used if any of the other allies show up, to keep Luke at full health so you never need to flip down if you don't want to.

Mission Planning gives you bonus (Righteous Purpose) activations as long as a side scheme has been defeated. If playing solo, I'd consider adding Defend Our City so you have a few more schemes to put into play, but we're already into the end game by the time we're considering Mission Planning.

Additional thoughts; a tough Hawkeye is a good way to deal with Cottonmouth if your nemesis pops up unexpecedly. H/E can take all three attacks, stay alive, and still be firing arrows everywhere while you mop up.