Just an idea I had: WI instead of having several daughters to marry with other nobles of Europe (eventually leading to Spain be inherited by a foreign dynasty) the Catholic Monarchs had instead a lot of sons? Let's assume that their issue would be something like this: John (born in 1470), Juana (1478), Ferdinand (1479), Henry (1482) and Alfonso (1485).
Obviously, Spain would remain under the Trastamaras. But what could be the effect of this change in the kingdoms where the OTL princesses were married: Portugal, England and the Habsburg Empire? Any ideas?