The only TPK I've had was in Living Greyhawk. I killed a party of L1s in a particularly nasty APL2 adventure. Other than that, a recent forray into the Slave Pits of the Undercity killed all but one PC. So technically not a TPK, but we quit there anyway.
Anyway, keeping a game going (especially in my homebrew, where games revolve around the PCs), is both difficult and annoying for both the players and myself once turnover reaches 50% or so. New PCs have difficulty fitting in, usually having no raison d'etre in regards to the current party. My last campaign in my homebrew, I tried to desperately finish, even though the three original players had all moved away. The newer PCs had less and less reason to care about what was happening, and it didn't end all that well. I could have moved in a different dirrection with the new PCs, but you might as well start over if you're going to do that, so you can truly focus on them.