As I have often seen suggested to create a larger native population with more influence, have Variola Minor (Alastrim) reach America and spread instead of Variola Major (Smallpox). Alastrim has less than a 1% fatality rate, compared to the 30% rate of Smallpox, and antibodies for it are equally effective against smallpox itself.
If we assumed that the ratio of Alastrim deaths to Smallpox deaths held true as a virgin soil epidemic AND variola pathogens were the only Eurasian pathogen involved, we'd have ~1/60th the plague deaths of OTL.
That needs to be adjusted, though, because whether smallpox or alastrim, variola was not alone in reaching America. My presumption, though, is that the reduction in death rates would actually be greater than division by sixty on account of both the lower death rate reducing the instances of the infected dieing because there was nobody healthy to care for them. Another reason for the reduction in death rate is that rather than someone being infected with influenza and smallpox, a recipe for sure death, they would be infected with influenza and variola, so mostly just influenza for the purposes of determining their chances of survival.
On another note, a spread of variola minor would likely prevent the massive population diebacks which made the civilizations of Mesoamerica and the Andes so fragile and vulnerable to conquistadores.