Which event in the history of Spanish and Portuguese empire-building in the Americas was the most significant?

In 1484 Christopher Columbus tried unsuccessfully to interest King John II of Portugal in voyages of discovery to the west. Columbus then offered his services in leading such an explatory voyage to King Ferdinand and Queen Isabella of what later became Spain. Queen Isabella in 1492 after the defeat of the last Muslim stronghold in Spain agreed to finance such a voyage and named Columbus as the admiral, viceroy and governor of any lands he should find. On August 3, 1492 Columbus' fleet of three ships left Spain and made landfall in the Bahamas on October 12th, about two months later. The fleet then sailed to the northeast coast of Cuba and turned to eastward to the island of Hispanola, which now contains the countries of Haiti and the Bominican Republic. There Columbus lost his flagship, the Santa Maria. He then returned to Spain to report his findings