According to Charles Ross – a respected historian, citing contemporary English and Spanish state papers – the ambassador to England of Isabella of Castile told Richard III that Isabella had been hostile to England because Richard’s brother, Edward IV, had turned down her marriage proposal to marry Elizabeth Woodville. (The timing works; Edward married in 1464, when Isabella was 13 years old, and she married Ferdinand five years later.)
The alternative histories virtually write themselves:
No marriage of Ferdinand and Isabella, no union of Aragon and Castile, no conquest of Granada, no expulsion of the Jews and the Moors, no Inquisition, no Charles V, no Habsburg empire, no Thirty Years War. Columbus might have sailed on behalf of England rather than Spain, or else his fellow-Genoese Giovanni Caboto (“John Cabot”) might have gotten to North America before any European found the West Indies.