Warning: This guide was prepared for game version number 21142 (it is the last version before introduction of "The Color of Madness" DLC) and now can be outdated. I will try to update it soon.

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My preferred all-around quirks
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Slayer (Eldritch / Beast / Man / Unholy) - Eldritch and Beasts are two types of our main enemies. Man and Unholy Slayers are less valuable but they still can find their use. There are also Hater variants, but for me +ACC is more valuable than +DMG - you will not damage enemy at all when you are not able to hit.

Quick Reflexes / Early Riser - +SPD is always good, especially for heroes with stuns and buffs. There are also "+SPD on first turn" quirks but I'm not a big fan of them as they can mess party strategy.

Clotter - There is a lot of bleeding in this game (and also Occultist can cause bleed on his heal).

Photomania / Steady - Stress reduction is always good to have. Photomania is much better quirk than Steady, but for no light runs Steady can also be used.

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My preferred quirks for specific functions
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Unyielding - good for healers and important characters

Hard Noggin - good for healers and guards

Hard Skinned - good for tanks with already high PROT value

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My preferred quirks for specific heroes
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Natural Swing / Corvid's Eye - good for Leper as he has probably lowest ACC in the game.

Eagle Eye - good for Arbalest to increase her highest CRIT in the game even more.

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My preferred quirks to lock on heroes
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note: no Flagellant / Shieldbreaker as I've not used any DLC yet

Abomination
- Photomania
- Steady
- Clotter

Main problem of Abomination is stress. He gets +stress every turn when transformed and returns to human form when reaching afflicted level. I think Photomania and Steady are the best quirks to prevent it. Abomination will not go in party with Vestal so Occultist will be almost always used - Clotter is good to have for such case.

Antiquarian
- Quick Reflexes
- Early Riser
- Unyielding

Antiquarian can use party buffs and can be used for death's door recovery.

Arbalest
- Eldritch Slayer
- Beast Slayer
- Eagle Eye

Eldritch / Beast Slayers for two most common enemies. Eagle Eye to increase her highest CRIT in the game even more.

Bounty Hunter
- Man Slayer
- Quick Reflexes
- Clotter

Man Slayer to increase effectiveness of his skills. He can be also used as support class (stun / pull) and as a part of marking party with Occultist.

Crusader
- Unholy Slayer
- Hard Skinned
- Unyielding

Unholy Slayer to increase effectiveness of his skills. He can be also used as tank and in death's door / stress recovery.

Grave Robber
- Eldritch Slayer
- Beast Slayer
- Quick Reflexes

Eldritch / Beast Slayers for two most common enemies, +SPD also helps.

Hellion
- Eldritch Slayer
- Beast Slayer
- Quick Reflexes

Eldritch / Beast Slayers for two most common enemies, +SPD also helps.

Highwayman
- Eldritch Slayer
- Beast Slayer
- Quick Reflexes

Eldritch / Beast Slayers for two most common enemies, +SPD also helps.

Houndmaster
- Beast Slayer
- Hard Noggin
- Quick Reflexes

Beast Slayer to increase effectiveness of his skills. He can also be used to guard so the more stun resist the better.

Jester
- Quick Reflexes
- Evasive
- Clotter

Jester can use party buffs and will be often used in party with Occultist and/or Abomination. Evasive is here to increase his highest dodge in the game even more.

Leper
- Eldritch Slayer
- Beast Slayer
- Natural Swing / Corvid's Eye

Eldritch / Beast Slayers for two most common enemies. Natural Swing as he has probably lowest ACC in the game. Corvid's Eye is much better than Natural Swing but it is also much harder to acquire.

Man-at-Arms
- Hard Noggin
- Hard Skinned
- Quick Reflexes

Man-at-Arms is a party buffer, stunner and guard.

Occultist
- Eldritch Slayer
- Quick Reflexes
- Unyielding

Eldritch Slayer to increase effectiveness of his skills. Occultist can be also used as main healer and/or party support.

Plague Doctor
- Quick Reflexes
- Early Riser
- Unyielding

Plague Doctor is the best stunner, can be used to cure status effects and for death's door recovery.

Vestal
- Hard Noggin
- Quick Reflexes
- Unyielding

Vestal is the strongest party healer.

Quite a lot of monsters in the main and hardest dungeons of the game (the Darkest Dungeon and the Courtyard) can cause bleed. Yes, bleed alone is not too dangerous but paired with critical hit (and sometimes also blight) can often lead to Death's Door and then to the death of the hero.