If somebody's bothering me IRL, I'll tell them calmly, "Please stop." If that doesn't work, I leave without really saying anything.
If it's on MSN or YIM or any form of messenger, I talk idly until I get bored and block them.
If it's in a game, like...let's say, Team Fortress 2, and I get flamed for using a particular weapon or being generally stupid (combat medic springs to mind) I reply with "Well, gee, I'm sorry for, y'know, having fun. Is the concept completely lost on you?"
I rarely tell people to fuck off because I'm a big coward. Ignoring them to death or using a simple retort is usually how I deal with it.