Anti-Climax Boss: Wager Master with his instant-win/loose conditions. The heroes can get powers, build themselves up, get all the combos they need and then Wager Master draws a card and the game instantly ends.
Best Boss Ever: Iron Legacy is brutal, does hideous damage and can be straight up overwhelming. But the theme of the character and the challenge makes him one of the more popular fights and it's incredibly satisfying when you manage to bring him down.
Best Level Ever: Time Cataclysm is a fan favorite thanks to Fixed Point. Making every card except itself indestructible opens up all kinds of shenanigans, ranging from putting out normally impossible combinations (mixing Mr. Fixer's tools or styles or multiple platings for Omnitron-X) to absurd amounts of damage (with Twist the Ether or Imbued Fire, Absolute Zero can put himself in an infinite-damage loop) to getting an extra free round out of Ongoings that either destroy themselves at the start of a turn or have a maintenance cost.
Game Breaker: No one character is capable of it on his own, but certain combinations can be incredibly potent, and certain cards can outright shut down villains in the right situation:
Haka's Savage Mana has the potential to take a lot of bite out of minion-heavy decks; by putting them under the card instead of in the trash, Voss's minions can't come back during Forced Deployment, Citizen Dawn may never flip, Baron Blade's Non Standard Game Over is curtailed, The Chairman's Prison Break does nothing, and the Matriarch's Darken the Sky brings nothing back from her trash. Apostate with his dependency on Relics (and his Relic spirits pulling them out of the trash) also gets hit hard.
Wraith's Infrared Eyepiece can make any villain deck almost trivial — if used every round, you can tightly control what cards are played. This means the cards listed under That One Attack never have to come up. And it's not Limited, so she can have — and with the Utility Belt, use — two at a time. In addition, using it lets you draw an extra card, which will eventually get you anything you might need.
Against The Chairman, Visionary's Brain Burn — which puts the villain's trash at the bottom of the villain's deck — turns him from a terrifying, tier-4 villain to almost a joke. So much of his strategy revolves around bringing Thug cards out of the trash that if they're not there — and won't be drawn from the deck for a while — he's screwed.
Absent an environment with Ongoing destruction, Visionary and Ra can completely shut down villains who do most, if not all, of their damage on their own, like Spite or Plague Rat. Ra can make the whole party immune to fire damage, while visionary's Twist the Ether lets her change the damage type of any one target. Ra can also change the party's damage type to fire, rendering self-damage cards, like Plague Rat's Infection, harmless.
The Unforgiving Wasteland Environment card is trouble for minion-heavy decks too, just like Haka's Savage Mana, causing any target destroyed by the environment to be removed from the game. The difference is that it's much harder for many villains to destroy, and most of the cryptids of the Final Wasteland target lowest HP enemies. Of course, it can easily break the game in the other direction too, and is the potential source of many Unwinnable scenarios for those poor heroes taking on villains that need to have cards in play or in the trash to beat.
Goddamned Boss: Kaargra Warfang has a reputation for being a real pain in the neck, due to the players having to juggle multiple additional mechanics while playing her (Favor pools, the Title deck, etc.), and having a very swingy game that often makes victory and defeat seem random rather than the result of her difficulty as an enemy. The digital version highlights the latter flaws by taking care of the former for the players.
That One Attack: Several boss decks, particularly those rated 3 or 4 in difficulty, have these.
The Chairman has Prison Break, which brings every Underboss in the trash back into play, who in turn each bring a thug back from the trash.
Grand Warlord Voss has Forced Deployment, which resurrects every minion in the trash at the start of his turn — this could easily bring a dozen damaging cards, many with global damage, back to the field if it pops up late in the game. If he's flipped to the wrong side at the time, it could easily mean his victory. And destroying it ahead of time just give you more time to react by playing the bad guys immediately.
Baron Blade and Omnitron each have a card that's this trope for set-up heavy heroes. Baron Blade's allows players to destroy as many equipment and ongoing cards as they want, and afterward he does every hero target X damage, where X equals 3 plus however many equipment cards are still on the table. This means either wiping your equipment and ongoings out, or everyone taking massive damage — it can easily become a Total Party Kill, especially in 5-hero games. Omnitron's outright destroys the equipment, and does damage to each hero based on how many of their equipment cards were destroyed at a rate of 2 to 1, which can be devastating to heroes like Bunker, The Wraith or Absolute Zero.
Apostate has Apocalypse which wipes the board of ongoing, environments and equipment. It also doesn't affect his relic cards so he effectively wipes away all the hero cards while he keeps his weapons.
Citizen Dawn has many.
Devastating Aurora, a card that destroys all hero equipment and ongoing cards as well as destroying environment cards. This one attack is able to completely turn an entire game around, especially if it fires while Dawn has several powerful minions out.
If Citizens Truth and Anvil are out, not only is all damage inflicted by the heroes reduced by two, but only Truth can be hurt. This effectively renders most damage dealing base powers impotent, and only high-powered cards can actually get through to even hurt Truth, who needs to get brought down before you can attack any other Citizen.
Rise With The Dawn doesn't do direct damage... it just brings out a Citizen from Dawn's trash. That minion you thought you were finally done with? They're back.
Citizens Blood, Sweat, and Tears, if they're out together. You'll be shedding ongoing cards like water, discarding multiple cards from hands, and taking heavy damage the entire time.
Look, let's be honest... when they least damaging cards Citizen Dawn can throw out are ones that let her draw more villain cards or damage the entire party and force them to discard cards, you know you've got a deck loaded with this trope.
The Matriarch has Darken the Sky, which brings out all of the Fowl cards in her trash. When considering the number of fowl she has and how fast you'll likely be burning through them, you could go form dealing with a few each turn to fight a dozen at a time.
Kaargra Warfang's Fickle Fans can instantly lose the game for the heroes because of Kaargra's Crowd Favor mechanics. It takes H favor from one pool and puts it into the other. If the heroes are in the lead and this card puts the villains over 20 favor, the heroes lose instantly. Can be subverted, because the card works both ways — savvy and prepared players can set it up so the heroes get the boost.
The Chairman stands above several of the other villains — even others rated at the highest difficulty, like he is — and can easily overwhelm players who don't know exactly how to handle him. Of his 25 cards, 10 are "Thug" cards, who do damage, destroy hero ongoing or equipment cards, protect the higher level minions, or play a villain card every time a hero card is played. Five of the other cards are "Underbosses," who buff the villains' damage, heal them, and revive the Thug cards at the end of each Villain turn. Players must keep the minions in check, because they will overwhelm your team if you don't...but each minion you destroy has The Operative attack one of the heroes for heavy damage. Each turn guarantees at least one Underboss play, and when you do start making real headway, Jailbreak can revive all the minions you've put down, and Undivided Attention will do severe damage to someone on your team. Oh, and The Chairman is invincible for most of the fight, and when you do get to hit him, he retaliates against the damage dealer for heavy damage, and buffs his Thugs' damage by up to +3, doubling most of their damage. Other villain decks have similar mechanics — Citizen Dawn's minions are just as much trouble and boost one another, while The Matriarch uses similar swarm and revival tactics while doing similar retaliatory damage — but The Chairman does it with a consistency and scale that is above and beyond the others.
Unlike every other villain, Spite's buffing cards — the drugs — are indestructible and cannot be removed from play once they're out. He also heals with every bit of damage he does on his front side and is constantly doing damage, making it hard to make anything stick. His victim cards — which heal him when he destroys them — tend to extract a substantial toll to be put under the Safe House, but Spite has cards to undo the hard work of getting them under there. Deck control is of limited use because he plays two cards a round — so even if you make sure he'll play a relatively harmless card at the middle of his turn, there's no real guarantee he won't play something like Drug Raid at the end of it. Even though he's rated at a 2, an unprepared team can have a mountain of trouble facing him. What saves him from being on The Chairman's level is the effects of his drugs include nerfed versions of normal effects — one gives him H-2 Damage Reduction, but only to the first hit a turn instead of permanent every hit; another makes the players put H-2 equipment or ongoing cards back into their hands, rather than destroying them — the fact he's the only damage dealer in his deck, so cards like Elbow Jab and Twist the Ether can hold him back significantly and the Potential Sidekick victim card, which lets the heroes draw two cards every villain turn as long as he's out. Other difficult villains, such as the Chairman and Iron Legacy, are generally seen as well-crafted challenges, but many on the game's forums feel that Spite is not very fun to play against and he's often accused of simply having poorly-designed game mechanics.
Spite's Agent of Gloom variant is another headache. He starts with all the Drug cards face down, and flips one face up at the start of his turn unless there are H victims in the safe house, in which case he flips instead. The variant opens the turn flipping one drug card face up (and the players don't know beforehand which is which), the Safe House puts a Victim into play and, at best, Spite plays another victim card, as the variant only plays one card per turn. The only way to flip a drug card face down again is to end Spite's turn with more victims in the safe house than there are drugs face up. Unless the players can force him to play an additional victim (i.e., if you're using one of the tiny handful of heroes who can do so, or if he plays the Good Samaritan, which can play the villain's top card to go in the safehouse), there's no way to outpace the drugs going face up before he flips and the flipped side has no mechanism to flip back or flip the drug cards. And on his flipped side? Every instance of his damage is boosted by 1 for every card under the Safe House, so if you're in a 5-hero game, he's doing obscene amounts of damage until you can get some of them back out.
One of the nastier elements of Miss Information is that for the most part, her clues cause the heroes to do damage to themselves. She effectively turns around damage-boosting powers and artifacts to hurt the heroes, and because a lot of the more powerful damage mitigating cards specify that they prevent damage from villain or environment targets and not heroes. Since her Clues are necessary to reveal her and get her to flip, the players have to deal with these devastating cards for some time before they can take her out. And because she's not a target until she flips, it becomes a waiting game for the clues to come out where the heroes have little option but to sit back and get hammered by her and the environment.
The Dreamer is a combination of the nastier mook swarm-based decks with the added caveat that the most effective minion-clearing abilities are often useless, as they most often target all villain targets, including the Dreamer herself, and the objective when fighting her is to keep her alive. Not only do you have to fight off packs of minions, but once you get the Dreamer to a flip to the side that will let you start knocking out minions to save her, she'll start hitting you with board-wipes that remove all hero ongoings as well as blasting your team with continuous psychic attacks every turn.
Iron Legacy. He has no minions. He has the lowest HP of any single villain aside from the Dreamer. He's just one target to hit. All he has is a non-stop onslaught of ongoing cards that reduce damage dealt to him, amplify damage dealt to heroes, and generally ruin your day. His damage output is so high that it's not implausible that you'll have downed heroes by the second turn. He's a terrifying example of a Legacy who isn't holding back.
La Capitan may be rated a 2, but her deck can be an irritating pain to deal with. Her ship, which starts the game in play and has a hefty 15 HP, both plays an extra card at the end of her turn and shuffles the villain deck at the start, makes most deck control useless and destroying her cards a much less-permanent setback. Her minions are each unique, and therefore have fairly high HP and do solid damage and/or have fairly powerful effects. She has cards that draw a certain amount of minions from her deck or her trash; worse yet, unlike Gloomweaver or Akash'Bhuta, whose cards say to reveal H cards and play whatever minions you find, La Capitan's cards instead have you search until you find H-2 or H-1 minions so you're all but guaranteed to have several come out unless you're lucky enough to get the trash search while they're all in her deck or vice versa. She has another card that can bring the ship out of the trash. She has an Ongoing card that does revenge damage to every hero target when one of her minions goes down. Her card says that any time the villains destroy a hero card, it goes under her, making the heroes' trash searches next to useless and allowing her to eventually flip and shrug off attacks while healing herself and her crew. The combination of these means without both good deck control and enough damage to deal with her ship quickly, it's very easy to simply be swarmed by her goons within a couple turns and lacking key Ongoing or Equipment cards to deal with her.
As environments go, Rook City is by far the least friendly to the heroes. Several cards buff the villains' damage and defenses or give the villains extra card plays. If you don't have environment destruction, you have to tolerate extra card plays for the environment or villain. With the exception of two cards — Tony Taurus, who scries the villain deck and Dr. Tremata, who scries the environment — the whole city works against you. Rook City can turn even the easiest villain into a nightmare.
While not nearly on the same scale as Rook City, Megalopolis can be a pain in its own way, with cards that prevent playing cards, drawing cards or using powers, and Cramped Quarters Combat changes all damage to Melee, a pain when you're playing a hero dependent on a damage type (like Absolute Zero or The Wraith) or up against enemies immune to it (Advanced Gloomweaver, Shu of the Ennead, Voss's ships).
The Ruins of Atlantis falls under this for one card: The Pillars of Hercules. While it has an upside for the heroes, adding an extra play, power and draw, the downside far outweighs it, as it lets the villain deck play a card at the start of every turn. Even if you decide to skip a turn to destroy it, it plays the villain card before the player can exercise that option, meaning you're getting at least two extra villain cards in play before you can do anything about it.