I’ve done it myself. What if an alien decides to attend college on Earth? What if a wizard ended up in a garage sale? (that one went in a different direction than I had planned) What if a meteor shower hid something else? (Hmm, I tend to use that one a lot).
Science fiction tends to rely on a number of ‘what if’s as basic. What if faster than light travel existed? (And FTL communication is possible). What if psi powers do exist? (That ‘what if’ started off in science fiction when I first started reading it, but now it seems to have migrated into fantasy.) What if there are other lifeforms in the universe?
Not only is ‘what if’ a good way to start the idea behind a story, it’s also a good way to continue or add threats or twists. Lois McMaster Bujold, for example, has her "worst-possible-thing guideline" (Sidelines: Talks and Essays, 2013) - i.e., "what is the worst possible thing I could do to this character?" For some YA and children's stories, this could be rephrased as "what is the most embarrassing thing I could do to this character?"
What are some 'What if?' triggers that you have used as a writer or enjoyed as a reader?