What happened to Juana was all fault of her husband and parents and would NOT happen to her if she had married differently to a better husband
Yeah, Manuel would have no interest in declaring Juana insane + judging from his OTL marriages he was a good husband.
Charles V spent his life on the road because he was simply unable to rule from one place alone, is all. But, Joanna could certainly try to rule Castile and Aragon from Portugal, it hasn't been done before.
Yeah, but Portugal is actually close at least to Castile, it's not that far. Union with Burgundy was actually harder to do, as Charles V's reign proves.