It's a simple but big question. How do you know when to put the characters down and fold up the GM screen and move on to a new game?
This is generally a harder question for fans of open-ended games than folks like, say, Bill Stoddard, who routinely run games with an arc of play and an end point.
But how do you know it's over barring a TPK that derails the game and ends interest in picking it back up?*
I know back in my elementary school/high school AD&D days, it was over after Q1 Queen of the Demonweb Pits. No campaign end party or anything. No plan. But that was the highest level module we had and if you beat it, we pretty much didn't have anything more to put in front of you. PCs made the occasional comeback, but even the one time we played the Q1 vets from one game it was in the elf-world behind one of the gates in Q1. It was a campaign ending finale.
Otherwise, we played until PCs died off or players moved on from lack of interest.
My later games sometimes had a clear end goal, but they were rarely met. The games still ended either from a TPK or a near TPK and a lack of interest in playing any further. My pirate game ended when the PCs got a ship and escaped, and while we talked about running a ship-based pirate game we'd had our fun in the "bust out of captivity and escape to freedom!" campaign.
My DF game, by design, can wrap up whenever we want to. It's pickup basketball, not a league with a championship game at the end. I have ideas on potential cool stopping points, but it's not meant to go out with a bang but just go on until we get bored.
Still it's hard to say for me when an open-ended campaign should end without a TPK. I can plan for it, but it's hard to set an end-point unless the game has a strong story to it, even if that story is just "get to power level X and do Y or establish in-game thing Z."
How about you guys? When do you know you've gotten the fun out of it and it should be put down?
* No, I am not saying all TPKs end games. I'm talking about the ones that do end the game as everyone says, that was fun, but let's start over with something else.