So far I've made two large mistakes (that i know of).
1. I used the fire-keeper soul you get from the gargoyles, instead of taking it to someone to reinforce my estus flasks (I am constantly punching myself in the face over that one).
2. I accidentally hit the female undead merchant in the little sewer shortcut, and now she won't talk to me.
English
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There's not much you can do about the firekeeper soul, but there are plenty more of them in the game. As for the female undead merchant, you can go to Velkas in the Belltower of the Undead Church to absolve your sins, and she will forgive you for attacking her.
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K, I'll go try that once I'm done in Blighttown.