There's two different versions of this question.
1) Your campaign is nearing its conclusion (like, all the PCs are level 20, their personal storylines have generally resolved, and they are coming up on the Big Bad who you expect to be the final antagonist before you do something else.)
2) Something goes awry, and the characters are in a situation such that the obvious natural conclusion is a complete campaign fail The moral equivalent of a TPK in games that have death).
My answers are (1) certainly, and (2) I will consider it, but it depends on how the players view that conclusion.
Stepping away from the question of motivation, just as allowing death for some adds a certain atmospheric spice to the game, not having death serves the purpose of not ending stories prematurely, or in an unsatisfying manner. If that unshceduled campaign failure is unsatisfying, then I probalby won't do it. If it is satisfying, then that's how it goes.
On number 2: Can you elaborate on this a bit? With the players you've had, what sorts of situations have they seen such a conclusion as acceptable? What situations have they not?
I guess I am just curious as to what other parties view as an Acceptable 'We screwed up, we lose' scenario. Does it entirely depend on if it creates a 'satisfying story'? Or can they accept the loss due to screw up/bad decisions even if it ends in an ignoble tragedy for the party?