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There were plans to marry the future Felipe II of Spain to Marguerite de Valois. Unfortunately due to the Franco-Habsburg rivalry flaring up again he married his Portuguese double first cousin (because it's the Habsburgs, plain first cousin just wouldn't do) and she remained a spinster until age 36 when she married the duke of Savoy (Felipe's other cousin).
But what if this match had gone through? No Don Carlos to contribute to the Black Legend, obviously, but what else?