Why end the Ultimate Universe? It's a new universe for a new (and the old) generation of fans to enjoy without all the old continuity issues getting in the way.
As long as the creators can keep it together and not fall into the same traps as before, it should just keep going.
Downfalls, should it come to that:
Too many ressurections. Main characters are an exception, they can be "ressurected". (I'd love to see Ultimate Beast come back... perhaps with ultimate Apocalypse?). However, smaller characters should just stay dead. (i.e. if they kill Ultimate Dazzler or Ultimate Kraven the Hunter... they're dead! End of story.)
Retconning. Except in the case of Ultimate Punisher because all they did with Ultimate Pun was half-arse update the origin and slap "Ultimate" in front of Punisher. I was hoping to see a much more organic Castle figure in the UU... without the spandex/kevlar bodysuit, more like the Punisher art on the cover of most of the Ennis issues for the last 5 or so years. And they can retcon the horrible O.S.Card Ultimate Iron Man, too, because that was a horrible waste of 6 months for me.
Overdoing it. I like the way they've paced the Ultimate Universe thusfar. We have a select number of Ultimate titles (Ultimates, UFF, UXM, USM, the minis *MINUS UIM!* and I suppose Ultimate Team-Up.). I'm sure they'll add more. Perhaps a non-Card penned Ultimate Iron Man, an Ultimate Captain America, maybe an Ultimate Hulk... but the day I see Ultimate Speedball or Ultimate Darkhawk on the shelves at my LCS is the day I'll give up hope. Until then...