Full stake existential threats -- whereupon we had all the panelists neatly agreeing that the soul of story is conflict, and threatening the life of the character and the existence of the world around him is a great way to get conflict going.
Though, actually, a lot of works are more on a personal level. Literary fiction for instance. Game of Thrones -- a lot of its audience is not watching it for the fate of kingdoms and worlds. They're watching for the fine-grained interactions and the individual politicking. . .
Whereupon someone brought up the line about how small minds talk about people, medium minds talk about events, and great minds talk about ideas. Some discussion about scope and Galactic Empires and the like. . .
One audience member brought up the problem of stakes being expected to be too high: you can't write an epic fantasy without world-shaking stakes and the hero being the one to shape the world. Some discussion about having a character finding a fit with the world he's in and the lack thereof in fantasy works -- though, as one panelist observed, you have literary fiction for that.