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Isabella's brother Alfonso, dies, making Isabella the next eligible heir and a potential pawn for the nobles in court
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Isabella marries Ferdinand II without her brother, Henry IV's approval
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Isabella and Ferdinand petitioned for the Spanish Inquisition, which was a popular movement against non-Christians in order to "purify the people of Spain" and basically killed off a good chunk of them
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An assassination against Ferdinand II was almost successful
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Isabella gives Columbus her permission to make a voyage to discover a new route to the Indies (ended up finding North America)
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A treaty between Spain and Portugal after Columbus found the Americas, where they separated the New World into two spheres. Spain acquired the right to discover and conquer everything from Brazil westward, while Portugal's sphere of influence encompassed everything east of Brazil.
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Isabella died due to a natural illness