That's the issue. Isabella and Ferdinand had already tried every means of disqualifying Afonso and failed. There are no excuses to pull out because they have already been exhausted. The only reason Portugal, Castille, and Aragon did not unify under House Aviz is because Afonso died under "mysterious" circumstances.
Afonso, Prince of Portugal, was born in 1475 as the only son and heir of King John. In 1490, Afonso was married to Isabella, the heir of Isabella I of Castille and Ferdinand II of Aragon.
The marriage of these two families created an interesting situation. If John, the only son of Ferdinand and Isabella, died without heir Afonso would be heir not only to the throne of Portugal but also to the thrones of Castile and Aragon. After realizing their mistake, Isabella and Ferdinand tried every diplomatic trick to annul the marriage.
Salvation came to the Catholic Monarchs in a mysterious accident, where Afonso was thrown from his horse and killed. The prince's death ended the threat to Castillian and Argonese independence. A later attempt to unify the three crowns under Manuel I of Portugal also failed.
So what if, Afonso had not been thrown from his horse and instead unified the three crowns into an Iberian Union?
Plus, the Prince of Asturias was still alive. At the time of the death of Afonso her wife stood at the very same position she stood on the day of their marriage the year before: behind the Prince of Asturias.You know, I always thought this was a kind of crazy conspiracy theory. So, the prince would be killed by orders of the same monarchs who only 5 years later would order their same daughter (who would be again their heir if John had died) to marry the new king of Portugal. It just makes no sense at all. If they didn't want the risk of their kingdoms being inherited by the Portuguese, they wouldn't marry her again to the Aviz. And I really never found any valid historical source pointing to any attempt by Ferdinando and Isabella to dissolve the wedding. I don't doubt it could have existed, but anyone has any more credible source than Wikipedia?