"little Suzie will be eaten by vampires." (And for the sake of the hypothetical, rescuing little Suzie is the point of this game.)
I would even go a step further. I would say "the result of this adventure will be that you rescue Suzie". Then, you can see how you make an adventure of it. That's kind of where I was going with that quote. If you agree on something like this, you shift the focus of the game from the goal to the way to get there. There is no longer the peril of failure, there is only "pretend peril". Suzie can be abducted in the first attack of the vampires, there will be a way to get her back. Suzie has already been transported to another town when you storm the vampires headquarters, but you find an address. And so on.
You could even go and throw everything around at the end (if all players agree on that), have her taken and turned, but you find a cage full of children that you can rescue instead, and with a new vampire, you have a focus for the next game.
On the other hand, if you do not agree on something like that, every player will have a different view on those things. Most often, that will be "if we don't rescue Suzie from that first attack, she will be dead, so there can't be any failure". Like what tutori had said earlier in this thread.
I don't think that you have to have paper villains. The peril for the characters can be quite real, as long as the players are in agreement of what are acceptable outcomes, and what is off limits. Character death, for me, for example is off limits, if it just comes from bad luck on the dice. Sacrifice is absolutely possible, as is stupidity. Though I usually tell the players, that their action is stupid and will most likely end up with their character being dead. The players then need to find a way to beat a more powerful villain, find his weakness, and so forth. If you kill off the characters left and right, you'll end up with a group of characters that don't really have anything to do with what you are doing, because they are simply the 5th generation of replacement characters ("would you care to join our noble quest?").