Before Isabella and Ferdinand became co-monarchs of Castile and Aragon, Isabella wasn't the initial heir-presumptive. That was her younger brother, Alfonso, Prince of Asturias. He was the figurehead of a noble rebellion against King Henry IV who wished to name his daughter, Joanna, as heir-presumptive. But there were rumors that Henry was impotent and that he wasn't Joanna's father (We don't know and never will if the last one is true). Before Alfonso's death in 1468 from either illness, poisoning or throat-slitting (take your pick), Henry arranged for him to marry Joanna.
To cut to the chase, what if Alfonso had survived to become ATL Alfonso XII of Castile? First, obviously, is that the Iberian peninsula would remain divided between Castile, Aragon and Portugal, but Isabella and Ferdinand II of Aragon weren't married yet, nor were Mary of Burgundy and Holy Roman Emperor Maximilian I (the ancestors of the the future Hapsburg monarchy).
I'll admit we don't know much about Alfonso compared to his siblings, but I'd imagine he'd have had a similar upbringing to Isabella and might share some traits with her. As for marriages, there is his proposed marriage to his half-niece, Joanna, but the whole basis of Alfonso and Isabella being named as heir presumptive to Henry IV was based on the rumor that Joanna was a bastard. If they married, it would probably be an acknowledgement that she was Henry IV's daughter, and, therefore, that Alfonso was a usurper and unworthy to be king.
So far, I see five major candidates:
* Joanna, daughter of Henry IV of Castile. (
https://en.wikipedia.org/wiki/Joanna_la_Beltraneja)
* Mary of Burgundy. (
https://en.wikipedia.org/wiki/Mary_of_Burgundy)
* Anne of France, eldest daughter of Louis XI of France. (
https://en.wikipedia.org/wiki/Anne_of_France)
* Anne of Savoy, eldest daughter of Amadeus IX of Savoy. (
https://en.wikipedia.org/wiki/Anne_of_Savoy)
* Joanna of Aragon, sister of Ferdinand II. (
https://en.wikipedia.org/wiki/Joanna_of_Aragon,_Queen_of_Naples)
Any thoughts?