doing too much dope in a shot; not enough to pass out and OD but enough to keep your heart pounding while you are laying there thinking you are going to die. that happened to me a few times and it ruins the rush.
also, when you have to go to work or do something important right after a shot. I like to just lay around and enjoy it. I would try to save it for after work but sometimes couldn't help myself (and then I would be pissed at myself after work, but if I tried to wait, I would be thinking about that dope the whole time I was working).
oh, and of course: getting arrested. my ex and I got arrested literally 5 minutes after we did a shot. huge buzzkill.
and I agree with the person who said having to go outside to smoke a cigarette. I understand why someone doesn't want people smoking in their house, but its kind of annoying to get stuck in the pattern of: do a line, go outside to smoke, repeat 10 times.