1. The Columbian Exchange, which led to the transfer of diseases from the Old World to the New World and the resulting decimation of the Native American population. Also, as a result of the Columbian Exchange, the Old World's population skyrocketed due to the introduction of new crops from the Americas.
2. Spain rose to be the greatest power in the world before exhausting their gold and silver supplies from the Americas that they had gotten from places like the Potosi. Spain's economy declined and going into the 1600s they were no longer as strong as they were.
3. The mestizo race, who were people of mixed Spanish and Native American ancestry became a thing.