As I mentioned previously, I've been enjoying Sentinels of the Multiverse.
To give some context for what I'm about to describe: The rule book actually gives difficulty ratings for the various villains. The base game contains two difficulty-1 villains and two difficulty-3 villains. I've beaten them all, though the difficulty-3 villains are, of course, harder.
The Rook City expansion contains two difficulty-2 villains and two difficulty-4 villains. One of the difficulty-2 villains, Plague Rat, does seem to go into that spot, though he's closer to the 3s than to the 1s, I think.
The other difficulty-2 villain, Spite, remains unthwarted, at least in any game that I've played against him. His Drug cards combo to make him a real pain. The most annoying is the one drug that reduces the first damage that he takes each turn. The way that the game normally plays, the best way to deal with that is to use a one-shot card to eat that, then use a power to do damage. However, Spite has another card that damages a hero whenever that hero uses a power, in addition to making that player mill 5 cards.
Spite has 5 of these things.
Strangely, one of Spite's Drug cards whose name I actually remember - Demon's Kiss - is the least annoying because it merely does damage to every Hero target. Yes, that's the good one.
In strategizing about this, I think that the best approach is actually to use a team of just 3 Heroes (the minimum), because his damage reduction card works at H-2, which would be 1. That way, rather than trying a one-two punch, each hero could just know that their damage is -1, with a +1 on there if they happen to hit twice in one turn.
The moral of the story is that I might just have to ignore the printed difficulty ratings. ;P