I ended the 2nd Edition game I ran in college with a session that was basically an extended epilogue, after the party had gotten the MacGuffin artifact they'd been after for a year or more of real time- and told them what happened to everybody and everything. They all enjoyed it, and added input for what their characters would do and what they'd like to have happen both before and during the session. It was a nice way to end things, and though I would have liked to have gone on with the game to run a couple of other adventures I had in mind, it just wasn't in the cards with people graduating and all.
My 3.0/3.5 games have ended in various ways; one was a TPK, another was a party implosion due to simmering conflicts boiling over in a party of Evil-aligned characters, another ended because of some weirdness resulting from draws from a variant Deck of Many Things, and still another ended because the players wanted to reset and try something new (we left those characters and that story unresolved, which is somewhat unfortunate). Meanwhile, the now-Epic game has been going for 5 years of real time all the way from 1st level up to the current 27th as of the end of last session. It's still going strong.
There is, however, one really obvious point to end the Epic game if we feel the desire to do so- for several years now the players and characters have been aware that on a particular date in the game world, a total solar eclipse will pass over a particular spot on a desolate island, and open a gate to the Abyss that allows demons to break several of the usual rules of planar travel and conduct for 24 hours. During this time, they are expected to invade the world with armies that are millions strong. After the most recent session, this invasion event is still about six months in the future, in game time; there's no telling how long in real time it will take to get there.
The Epic PCs are resolved to be there to fight this calamity, if they can't somehow prevent it from occurring entirely, and for my part I've always planned to make the sessions dealing with that event very special. Back before the "beta" game ended for the first time (with the TPK), I had intended the "invasion" games to be marathon sessions where both parties would be brought together and face the darkness as one, but now after the "beta" game has had multiple endings and several characters left in limbo I suppose I'd just let people join the fun with whatever characters they wanted to bring back. Obviously, once the invasion ends, for better or worse, it's a great time to give the game(s) an epilogue and end a campaign.
Which is not to say that I don't have ideas for how to run adventures past the invasion- I could easily continue storylines after it. But I doubt anything will top it. And so, if the players want to end at that point, we'll end it and be satisfied, I think.