** Bokrug is one of the easiest Ancient One in the game. His Doom Track is relatively forgiving, and if you're diligent killing monsters and closing gates you can get rid of the four Beings of Ib before he awakens, which leaves him with very little means to screw you over in a significant manner, as his normal attacks don't actually hurt the players. Additionally, one of his Sinister Plots makes him turn around and [[ScrewThisImOuttaHere go back to sleep]], ending the game in ([[AntiClimax an admittedly anticlimactic]]) victory for the Investigators.
** Yig has been statistically one of the easiest to defeat Ancient Ones, even between different versions of him. In fact, he's recommended for players wanting a quicker game.
** [[UnskilledButStrong Ithaqua]]. He doesn't have too many checks you have to pass, and the battle is basically a straight-up physical brawl. If you use Call Ancient One when you're armed to the teeth, you have a shot at taking him out. Some players will swear by this method and not even bother closing gates if Ithaqua is the Ancient One.
** Azathoth, despite his RocksFallEveryoneDies nature, is still fairly easy to beat, as he takes a long time to wake up, has a very minor game-affecting ability, and sealing gates tends to be the most common way to win. He's often recommended as a [[WarmUpBoss beginner boss]] because he provides few special effects to worry about. This allows beginners to learn game mechanics and understand how to play.
** The Hound of Tindalos; it's one of the few monsters that can attack you in any location, can move anywhere on the board, and if playing a low sanity character (poor Monterey Jack), it's almost impossible to fight as it will just nuke your brain instantly.
** Plain ol' ghosts from the main game also count. They're immobile, not to mention ''immune to physical attack'' and have hefty penalties on Will, Fight, and Sneak checks. In the wrong place against an ill-equipped character, they are a formidable roadblock.
** Dholes. Resistance to both stats, lethal damage, high stats and toughness...the only thing keeping you sane is that it moves normally, meaning you can generally walk around it.
* GameBreaker: Despite the game's punishing difficulty, some investigators can really stick it to the Ancient Ones.
** Mandy Thompson is undeniably the strongest investigator in the original game and arguably even with expansions included. She starts with 4 clue tokens, which lets her seal a gate earlier than usual, and more importantly, her ability allows any one investigator per turn to reroll failed dice in a skill check. Any chance of being screwed over by bad dice rolls, whether in sealing a gate, killing a monster, or passing a risky event, can be remedied once every turn. She's only somewhat mitigated by her rather high-stakes personal story and low stats.
** Patrice Hathaway and Akachi Onyele work very well together. Patrice allows other players to use her clue tokens and Akachi takes one less clue token to seal gates. Meaning that with a little luck, Akachi can almost continuously seal gates with Patrice's support. Furthermore, Akachi's Personal Story showers the board with clue tokens for Patrice to pick up. They're powerful alone but together they make the game a cakewalk.
** Patrice herself. In an online count of statistics, Patrice ties with Mandy as investigators that have successfully beaten a game (with or without other people). Though it makes sense in a game about working together to defeat the board, that the most powerful investigators are the support characters.
* GoddamnedBats: Depending on the Ancient One, Cultists can be either this or DemonicSpiders. Expansions introduce other enemies that are also treated as Cultists and gain the Ancient One's special boons, thus making more bats to cut through.
** Some enemies have the "Endless" modifier, meaning they cannot be taken as a trophy. These enemies are usually easy to kill. USUALLY.
** Great Cthulhu himself. His cultists affect your sanity like most other monsters. Everyone permanently loses a point of maximum health and sanity with him in play. In the final battle, he regenerates a doom token after every attack.
** Atlach-Nacha is the most feared Ancient One in the game, and for good reason; sealing gates, the main method of defeating the Great Old Ones, barely inconveniences him at all. He is also extremely difficult to defeat once he awakens (though not impossible like Azathoth), with resistance to all damage and an ability that eats one Investigator or ally per round... and a card that can destroy all allies or target the player with the most items.
** Glaaki, with all expansions in play, is often considered Atlach-Nacha's stiffest competition for the top spot. Its five unique minions drain the party's supply of items and tokens, it can instantly put them back in play during the final battle, and it feeds on the rapid Terror Track growth of many expansions with its ability to devour all investigators if the track goes above 10.