Power failure, communications problem, runway incursion, hijacker in cockpit (saw that in a Clint Eastwood movie!). Since the pilot is responsible for what the plane does, then if in his judgement any damn thing means he should not take to the air, he should not.
41 years ago this month, a full 737 hit a block from my house. With at least 3 qualified pilots in cockpit, it still hit a Cessna. So you just never know.