My big things that will end something:
Pet waste anywhere it shouldn't be. I don't care if it's the hallway, the master bedroom that I won't be going into, a back corner of the living room. If it's not outside or in a litter pan, it's a no go.
Smoking. I'll tolerate it when I'm visiting for an evening with some people, but not overnight. It bothers my throat so badly I wake up sounding like I've screamed nonstop for the past week.
Access to a bathroom. If you've got a three story house and a family of 6 and one working bathroom, I'll have to really consider if it's worth it to me to stay there. I'm not saying I need my own, I just don't have to navigate two staircases and fight for time with 6 other people.
Pets being ill-behaved. I don't mind sharing a bed with a pet, so long as the bed is big enough. I don't mind pets coming to say hi to me. But I don't like cats that sleep on people's heads, or nibble their fingers in the morning to be let out, or any animal that's going to jump up on me and not listen when I say no or down. Enthusiasm is one thing, my dog is the craziest thing I've met, but at least she listens.
Unruly children. A friend of mine has her nephew living with their family. He throws things, screams all the time, grinds food into the carpet, and they don't punish him because "He's special, you know. He's been diagnosed. He has issues." This may be the case, but he can still be disciplined and trained to behave himself.
General uncleanliness. If there's flies and gnats all over your kitchen and dishes piled up all over the sink and counters and leftovers sitting out from the day before, I'm gone. And I won't be coming back for any meals any time soon either.
Honestly, though, most of the time I'm staying as a houseguest, I've had great experiences.