My questions are:I'll just answer the first question.
1. Are there any particularly brutal combinations of cards that I should avoid using in the same game?
2. Are there any particularly interesting combinations of cards that I should definitely use in the same game?
3. Is there an obvious difficulty order to the Schemes, from easiest to hardest?
4. Has anyone else done this, and if so how did it go?
The Legacy Virus
Setup: 8 Twists. Wound stack holds 6 Wounds per player.
Twist: Each player reveals a Tech Hero or gains a Wound.
Evil Wins: If the Wound stack runs out.Commentary: Play without Tech Heroes? Good luck. Play with them? (Forge, Iron Man.) Meh.
Midtown Bank Robbery
Setup: 8 Twists. 12 total Bystanders in the Villain Deck.
Special Rules: Each Villain gets +1 Attack for each Bystander it has.
Twist: Any Villain in the Bank captures 2 Bystanders. Then play the top card of the Villain Deck.
Evil Wins: When 8 Bystanders are carried away by escaping Villains. Commentary: Play with Black Widow or Jean Grey? Easy Peasy. Play without them? Um. Play against Mr. Sinister? Interesting. Play with Deadpool? LOL.
Negative Zone Prison Breakout
Setup: 8 Twists. Add an extra Henchman group to the Villain Deck.
Twist: Play the top 2 cards of the Villain Deck.
Evil Wins: If 12 Villains escape.Commentary: Up the difficulty by playing with Radiation, the Marauders, the Kree Starforce, or the Emissaries of Evil. Maggia Goons for easier, Phalanx for harder.
Portals to Dark Dimension
Setup: 7 Twists. Each Twist is a Dark Portal.
Twist 1: Put the Dark Portal above the Mastermind. The Mastermind gets +1 Attack.
Twists 2-6: Put the Dark Portal in the leftmost city space that doesn't yet have a Dark Portal. Villains in that city space get +1 Attack.
Twist 7: Evil Wins! Commentary: Straightforward no matter who you are. Bribe makes this easier, so avoid Streets of New York if you want a challenge.
Replace Earth's Leaders with Killbots
Setup: 5 Twists. 3 additional Twists next to this Scheme. 18 total Bystanders in the Villain Deck.
Special Rules: Bystanders in the Villain Deck count as Killbot Villains, with Attack equal to the number of Twists next to this Scheme.
Twist: Put the Twist next to this Scheme.
Evil Wins: If 5 "Killbots" escape.Commentary: See above for Bystander fun, i.e. Mister Sinister, Jean Grey, Deadpool, and Black Widow. I'm fond, thematically, of Skrulls here, if it were not for your restriction and the scheme below.
Secret Invasion of the Skrull Shapeshifters
Setup: 8 Twists. 6 Heroes. Skrull Villain Group required. Shuffle 12 random Heroes from the Hero Deck into the Villain Deck.
Special Rules: Heroes in the Villain Deck count as Skrull Villains with Attack equal to the Hero's Cost +2. If you defeat that Hero, you gain it.
Twist: The highest-cost Hero from the HQ moves into the Sewers as a Skrull Villain, as above.
Evil Wins: If 6 Heroes get into the Escaped Villains pile.Commentary: Spider-Man is deceptively tricky here since you don't have enough low-cost Heroes. Elektra, Colossus, Iron Fist would make this relatively easier, though. Direct attack, synergy, and low-cost Hero cards.
Super Hero Civil War
Setup: For 2-3 players, use 8 Twists. For 4-5 players, use 5 Twists. If only 2 players, use only 4 Heroes in the Hero Deck.
Twist: KO all the Heroes in the HQ.
Evil Wins: If the Hero Deck runs out.Commentary: Bishop, other deck thinners, make this easier---if you're lucky on the flop.
Unleash the Power of the Cosmic Cube
Setup: 8 Twists.
Twist: Put the Twist next to this Scheme.
Twist 5-6: Each player gains a Wound.
Twist 7: Each player gains 3 Wounds.
Twist 8: Evil Wins!Commentary: Meh. Play with Loki but no Strength heroes, or Apocalypse. Tier One Masterminds need only apply.
== Dark City ==
Capture Baby Hope
Setup: 8 Twists. Put a token on this Scheme to represent the baby, Hope Summers.
Twist: If a Villain has the baby, that Villain escapes. Otherwise, the baby is captured by the closest Villain to the Villain Deck. (If there are no Villains, do nothing.)
Special Rules: The Villain with the baby gets +4 Attack. If you defeat that Villain, rescue the baby to your Victory Pile (until the next Twist). The baby is worth 6 VP at the end of the game. If a Villain escapes with the baby, stack a Twist next to the Mastermind and return the baby to this Scheme card.
Evil Wins: When there are 3 Twists stacked next to the Mastermind.Commentary: Fun scheme, but no particulars spring to mind. Go thematic! Jean Grey/Cyclops, &c.
Detonate the Helicarrier
Setup: 8 Twists. 6 Heroes in the Hero Deck.
Special Rules: Whenever a Hero is KO'd from the HQ, turn that Hero face down on that HQ space, representing an Explosion on the Helicarrier. When an HQ space has 6 Explosions, that space is Destroyed and can't hold Heroes anymore.
Twist: Stack this Twist next to the Scheme. Then for each Twist in that stack, KO the leftmost Hero in the HQ and immediately refill that space.
Evil Wins: When all HQ spaces are Destroyed or the Hero Deck runs out. Commentary: Fun scheme, but no particulars spring to mind. Go thematic!
Massive Earthquake Generator
Setup: 8 Twists.
Twist: Each player reveals a Strength Hero or KOs the top card of their deck.
Evil Wins: When the number of non grey Heroes in the KO pile is 3 times the number of players.Commentary: Play no Strength heroes.
Organized Crime Wave
Setup: 8 Twists. Include 10 Maggia Goons as one of the Henchman Groups.
Special Rules: Goons also have the ability "Ambush: Play another card from the Villain Deck."
Twist: Each Goon in the city escapes. Shuffle all Goons from each players' Victory Piles into the Villain Deck.
Evil Wins: When 5 Goons escape.Commentary: Try Hydra. Don't look at the cards in advance!
Setup: 8 Twists. 24 Bystanders in the Hero Deck. (1 player: 12 Bystanders in the Hero Deck)
Special Rules: You may spend 2 Recruit to rescue a Bystander from the HQ.
Twist: KO all Bystanders in the HQ. Then each player reveals an Instinct Hero or KOs a Bystander from their Victory Pile.
Evil Wins: When the number of Bystanders KO'd and/or carried off is 4 times the number of players.Commentary: Use Heroes without recruit symbols! Black Widow, Hulk, Hawkeye, Iron Man, Nick Fury, Wolverine, Groot, Star-Lord. (People who know these decks, one in particular: Shh, no spoilers ... !)
Steal the Weaponized Plutonium
Setup: 8 Twists representing Plutonium. Add an extra Villain Group.
Twist: This Plutonium is captured by the closest Villain to the Villain Deck. If there are no Villains in the city, KO this Plutonium. Either way, play another card from the Villain Deck.
Special Rules: Each Villain gets +1 Attack for each Plutonium it has. When a Villain with any Plutonium is defeated, shuffle that Plutonium back into the Villain Deck.
Evil Wins: When 4 Plutonium have been carried off by Villains.Commentary: Again, consider especially the Radiation, the Marauders, the Kree Starforce, or the Emissaries of Evil.
Transform Citizens Into Demons
Setup: 8 Twists. Villain Deck includes 14 extra Jean Grey cards and no Bystanders.
Twist: Stack 5 Bystanders face down next to the Scheme. Bystanders stacked here are "Demon Goblin" Villains. They have 2 Attack. Players can fight these Demon Goblins to rescue them as Bystanders.
Special Rules: Each Jean Grey card counts as a "Goblin Queen" Villain. It's worth 4 VP. It has Attack equal to its Cost plus the number of Demon Goblins stacked next to the Scheme.
Evil Wins: When 4 Goblin Queen cards escape.Commentary: Use Recruit-heavy decks, especially Thor and Gamora.
Setup: 8 Twists. Villain Deck includes 14 cards for an extra Hero and no Bystanders.
Special Rules: Whenever you play a Hero from the Villain Deck, that Hero is captured by the closest enemy to the Villain Deck. Each Villain gets +2 Attack for each Hero it has. When you fight an enemy, gain all the Heroes captured by that enemy.
Twist: KO all Heroes captured by enemies. Then play another card from the Villain Deck.
Evil Wins: 9 non grey Heroes are KO'd or carried off.Commentary: Phalanx especially but no Tech heroes!
Forge the Infinity Gauntlet
Setup: 8 Twists. Always include the Infinity Gems Villain Group.
Twist: Starting to your left and going clockwise, the first player with an Infinity Gem Artifact card in play or in their discard pile chooses on of those Infinity Gems to enter the city. Then put a Shard on each Infinity Gem in the city.
Evil Wins: When 6 Infinity Gem Villains are in the city and/or the Escape Pile.
Evil Wins: When a player controls 4 Infinity Gem Artifacts, that player is corrupted by power. That player wins, Evil wins, and all other players lose.Commentary: Use Spider-Man. He's weak without some of the expansions you don't have yet!
Intergalactic Kree Nega-Bomb
Setup: 8 Twists. Make a face down 'Nega-Bomb Deck' of 6 Bystanders.
Twist: Shuffle this Twist into the Nega-Bomb Deck. Then reveal a random card from that deck. If it's a Bystander, rescue it. If it's a Twist, KO it, KO all Heroes from the HQ, and each player gains a Wound.
Evil Wins: When 16 non-grey Heroes are in the KO pile.Commentary: Bit nasty no matter what.
The Kree-Skrull War
Setup: 8 Twists. Always include Kree Starforce and Skrull Villain Groups.
Twists 1-7: All Kree and Skrulls escape from the city. Then, if there are more Kree than Skrulls in the Escape Pile, stack this Twist next to the Mastermind as a Kree Conquest. If there are more Skrulls than Kree in the Escape Pile, stack this Twist next to the Villain Deck as a Skrull Conquest.
Twist 8: Stack this Twist on the side with the most Conquests.
Evil Wins: When there are 4 Kree Conquests or 4 Skrull Conquests.Commentary: Bit simple no matter what, especially with Heroes who move Villains around, i.e. Blade, if memory recalls.
Unite the Shards
Setup: 30 Shards in the supply. Twists equal to the number of players plus 5.
Twist: Stack this Twist next to the Scheme. Then for each Twist in that stack, the Mastermind gains a Shard.
Special Rules: During your turn, any number of times, you may spend 2 Recruit to gain one of the Mastermind's Shards.
Evil Wins: When the Mastermind has 10 Shards or when there are no more Shards in the supply.Commentary: Attack-heavy deck, as above. Black Widow, Hulk, Hawkeye, Iron Man, Nick Fury, Wolverine, Groot, Star-Lord. (Again, people who know these decks, one in particular: Shh, no spoilers ... !)