The European disease issue is tricky. B/c under all the colonial schemes disease was the main killer. Most of the killings in the Mexico conquest initially were native group on native group. It was people who hated the Mexica aligning with with Cortes or taking advantage of the chaos to rebel. But after that, disease went through and killed in large numbers, usually around 30% under all the colonies, and then mismanagement, refusal to grant medical help, reservations and encomienda, forced labor and migration, killed another 60% under all the colonial systems.

But Spain and Portugal had a different legal underpinning to their colonies. The Treaty of Tordesillas required them to Christianize the inhabits and made them subjects of their respective crowns. In the English colonies the inhabitants were foreign peoples. They weren't subjects of the British crown and their land had to be bought or claimed through a doctrine of discovery. This led the Spanish to try to integrate native peoples into the colonies through the encomienda system. Where as the English, and later American and Canadians, needed to push them off of land b/c they were foreign elements, and therefore dangerous.

That doesn't mean the Spanish weren't incredibly cruel. In letters from 1502 and 1503 the Spanish Crown limited enslaving and punishing the native inhabitants but made exceptions for mining, but also for people who wouldn't convert, especially if they practiced cannibalism, human sacrifice, or witchcraft. That became a handy accusation for conquistadors to enslave the indigenous population. But it was limited by the indigenous people's ability to seek atonement with the religious authorities. There was nothing similar in the English colonies. The abuses were somewhat mitigated in the Spanish Colonies in 1512 with the Laws of Burgos.

Both systems conducted a genocide. But the Spanish genocide focused more on cultural elements. By the 1800s, if you look at the battles against indigenous people in Yucatan by the Spanish and in California or Texas by Americans, you can see the difference. The Americans were fighting wars of extermination. The Spanish, and later Mexicans, were fighting for political and cultural control. That's why you have these indigenous communities that are large practiced their rites in secret in Mexico and lived with Spanish descendants in their communities and smaller groups who were isolated from the American/Canadian settlers on reservations, but groups who were able to retain more of their indigenous culture in the US and Canadian systems..

There's a good book on the two different legal theories underpinning colonialism by Robert Miller called Native America, Discovered and Conquered.