Anything that reads as untrue to the character will irritate me. Once a writer establishes a character's ... um ... character, then let them have reactions and do things that sync with their established character.
If the characters do completely stupid things that no rational person would do, I get really irritated. I mean, really: There's an insane axe murderer escapee from the asylum half a mile away and the tstl heroine is home alone and hears glass breaking in her basement during a thunderstorm after the power goes out. She doesn't have a flashlight or a cell phone and all of her house phones are cordless and don't work when the power's out. But she decides to go down into the basement in skimpy pajamas and bare feet, unarmed, to see what that noise was.
All I can think is, "I hope she gets killed. She's an idiot."
I'm also distracted by:
Poor attempts at accents and 'folksy' speech patterns attributed to people from the South.
Those damned phonetically spelled words that are supposed to make us 'read' in that accent drive me crazy. I've never heard anyone ever in my entire life say, "Ah shore do thank yur a purtty li'l honey-child."
Flaws in adhering to the logic and established mythology of the writer's 'world'.
I read a book once that referred to events that were NEVER IN THE BOOK. And these weren't events that supposedly happened prior to the story's start. Something like, "She passed the door to the porch, shuddering at the memory of the butler's lifeless body hanging from the chandelier." The butler had never been mentioned since he opened the door at the beginning of the book, and certainly nothing was told about him being hung from the chandelier.
Also, illogical time warps. In that same book, it was established at the beginning, everyone in her family died on their 26th birthday and her 26th birthday was only a couple of weeks away. The book drags on and months pass, but her 26th birthday is still a couple of weeks away by the end of the book.
Ultra-fiesty heroines and inordinately wise kids as well as bratty kids will also ruin the story for me.
Errors in medical procedures, settings and such. I was a nurse for over 20 years. I know when they've screwed up.