If instead of landing in the Bahamas and encountering the primitive and peaceful Taino people he instead landed in southern Mexico and encountered the more advanced and more warlike Aztec civilization.
Let's assume he at least makes it back to Spain alive after this encounter.
Hmm... Well the exposure to European diseases would kill a lot of Azetcs earlier than in RL, conversely I expect syphilis to be imported to Europe by Chris's boys like in RL.
The difference here is that the Aztecs, and the various tribes around them will have more time to absorb the damage and rebuild, while the rest of Spain learns of the 'savage' Empire on the other end of the world. Spain (and the rest of Europe) lack the means to launch a full-scale invasion of a civilization across the Atlantic ocean, so they would be forced to approach this very carefully, IF Columbus also brought back SOMETHING to show the Spanish court that any return trip to 'Asia' like this would be worth it.
Considering the POD involves his meeting with the Aztecs resulting in him fleeing for some reason, I doubt he'd have had the chance to collect much in the way of trade-goods.
Plus... If we assume that Columbus was forced to flee quickly, this implies that there was some sort of fight, some of his men died, others captured, and he might have only been able to leave with one or two ships.
So there'd be some things left behind for the Aztecs to poke at, maybe even improve their tech-base a bit, which would make them even more dangerous fighters against the various tribes around them that HATE them for the endless Flower Wars and human sacrifice.
This is one of the reasons why (in RL) a handful of Spanish explorers were able to beat a civilization of millions of people, all the other tribes and nations around the Aztec Empire HATED THEM and worked to help the Spanish destroy the Aztecs.
In this POD? It might be awhile before anyone in Europe works up the nerve to launch a second expedition. Who wants to go to a land of hot, humid jungles where a highly advanced civilization is filled with warriors wearing animal pelts that will capture you and sacrifice you to their demon-gods? Especially if Columbus fails to bring back anything of material value...