If he loses to JDS again in brutal fashion, where does he go from there? It would be near impossible to get another title shot, and I don't think Velasquez is content with being 2nd best in the world. Moving down would be the best alternative if he cannot obtain the heavyweight title.
He stays at HW, destroys more contenders until he gets another shot and fulfils his goal. In such a scenario, it won't be close to guaranteed that JDS would still be the champion. If Overeem were to beat JDS, which is a definite possibility, then Cain could fight against a different champion in Overeem.
I hate it when fighters move from their natural weight class because they lose twice against the same guy in their current division. To me, that's just giving up. You don't stop or give in until you overcome that challenge.