Three is the magic number for me. Here's what I mean:-
(1) I get very annoyed when I have to explain the same thing for the third time;
(2) I also get very annoyed by the third time people repeat themselves when explaining things to me, without me expressing that I did not understand the first two times;
(3) When people make a comment at me that I can't tell whether it's personal, I give it till the third time, then perhaps it is personal;
(4) If a person flaked out on any lunch/activity plans by the third time, maybe he/she just does not want to hang out any more. Sometimes you just have to take the hints.
*(5) Most marriage can survive a partner being unfaithful at least once, but if cheating is an issue for you, then by the third time he cheated on you and promised it'll never happen again, think twice.
*(6) The same applies to an abusive relationship, by the third time he hit you and promised that he will never do it again, dump the a-hole!
Everybody must have a bottom line and learn when to put their foot down and say, "That's enough."
On point (5) and (6), I personally think once is too much, but most people are more forgiving than me.