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Most stress release limitors isn't too bad, just look out for combinations, like Gambler/Bad Gambler (why isn't there a Card Shark or something) and location based stuff depends on the classes (Cove Phobe is fine on a Jester, but terrible on an occcultist).
The worst ones are, of course, any permanent stat reduction quirk.
Particularly sneaky is the stuff that makes you trigger good-loot containers in ways which can hit you with a disease or something.
There's a list of all that stuff and what each one means on a wiki somewhere, and someone really ougth to make a properly powergamy list of stuff you just don't want discovering on your guys mid-run.
The other good set of negative quirks to get are the light-related quirks. Try and get low-light quirks (25 and lower) on a hero if you don't do dark runs. Conversely, a debuff at 75+ won't effect a hero you plan to use for dark runs.
Like others have said, Bad Gambler isn't horrible if the same hero can use other destress methods. I generally don't have a problem if a hero has a quirk that only allows them to use on destress method either. It's only really inconvenient before you upgrade your buildings.
Yes, I am serious. They:
1. Must be the correct type of curio
2. Must wind up being a negative turn out on that curio to even matter
3. Are not even guaranteed to trigger upon encountering that curio
4. Can be resisted if it's disease/bleed/blight negative penalty.
5. Most curios(probably 80% of them) have either low odds of negative outcome or the negative outcomes are minor things that a bandage or antivenom will fix.
So combine all of those things, and the odds that they even matter is pretty low. I would take some of them more seriously than others(Kleptomaniac, Confessionals, Iron Maidens, or Eldritch Carvings), but they're still pretty minor. Stat penalties are infinitely worse.
Some dope gets the one where he likes to go into confession booths. You brought the holy water specifically because there's a curio in there which lets you destress a guy mid-run, and the idiot does the opposite and goes nuts. Or the urn in the ruins? You brought some holy water to turn it into a big bunch of jewels? Too bad, here's a disease. Or you're carrying medicinal herbs around in the ruins just because the iron maiden gives loot for those - NOPE have some claustrophobia.
You're in a long weald run, so you brought medicinal herbs so that you can get food off of animal carcases? Screw you! Wanna clear a locked in -5 spd -5 dodge on the first turn? Here's some stress instead. Those bones in the warrens which you pour holy water on for loot? Have some stress instead! +30 damage until rest (stackable, stack a few, never rest) for some herbs? NOPE! The damned graves are actually worth sacrificing a shovel for, but no, here's a disease instead! It goes on and on and on and on...
Only quirk of that sort which is acceptible is one which makes guys open sacks and backpacks, because other than getting bad loot because it was done at bright light nothing can go wrong.
Otherwise, the game is more about handling the various curios exactly right and walking out with the most cash than it is about combat. You can pretty much "script" combat during preparation (only thing that really screws you up is random crit spam and surprise shuffling), but you really don't want anything interfering with the damned curios.