Sirens
It most likely means that somebody has been doing something stupid. I don't really want to wait around giving witness statements and such.

Stuff Starts Breaking
If stuff is breaking around you, that means people are getting way out of hand. It won't be long before people start breaking OTHER people so I take this as my cue to leave.

The Booze Is Gone
Once the alcohol is gone, a party generally loses it's steam. At that point, I make my farewells and hit the door.

Best Friend Is Crying/Puking/Yelling
If this is happening your friend has had too much. Too much beer, bullshit or drama. It doesn't matter. At this point, your friendly duty is to get them out of there.

Trouble Walks In
If you are at a party and your ex or enemy walks in...leave. It makes everything uncomfortable because then everyone at the party has to choose sides (who to talk to, what not to say, etc). This will ruin a party. Be the bigger person. This rule applies to your friend/wingman/bff too.