How might the War of the Castilian Succession have turned out if Juana la Beltraneja had turned out a son by her husband, Afonso V of Portugal?
Assuming they still lose, the final peace treaty would be rather different. For one, Afonso is unlikely to separate from La Beltraneja, place her in a monastery or countenance her betrothal to the eldest son of Isabella. I imagine peace would be a lot harder to achieve - now there is a young prince of Asturias for Beltraneja's followers (and Portuguese support) to rally around, while it will be a few years before Isabella produces a son. Presumably Afonso would be more vigorous asserting the rights of his young son versus those of his niece-wife. If so, the French might be more forthcoming in meddling in Navarra; if La Beltraneja was able to produce a daughter after her son, the girl would make a nice match for Louis XI's only grandson Charles of Clermont.
La Beltraneja is forever a danger to Isabella and Ferdinand while she is Queen consort of Portugal, just as Isabella would forever be a danger to La Beltraneja (as Queen of Castille) so long as she was Queen consort of Aragón. A double marriage between their children would be the ideal solution.
The results for Portuguese and Castilian colonial affairs, re: Guinea, re: the Atlantic, might also have significant repercussions on the development of the colonial period, the discovery/exploration/settlement of Africa and the New World, international law, the Catholic church and in due time the Reformation.