Well I was thinking the hostility would be caused by the INVASION not the diseases, and the earlier dissemination of infectious illness was more a way of allowing the Pre Columbian states to have recovered somewhat before fighting off Spain etc. Sorry if that was unclear.
I hardly think Europeans would be seen as invaders immediately. Unless they start randomly attacking people asking for gold/chopping heathen's heads off to convert them to Christianity, so that's just Spain/maybe Portugal.
And then there's also the matter of neither the Iroquois or Aztec existing since this would be a POD predating the formation of either polity. Although it's possible the Iroquois Confederacy might form anyway, and a state comparable to the Aztecs rises as well.
@metalinvader665 , the colonization of the Americas and access to its resources significantly boosted the power of the European nations. This made it much easier for them to rise to a position of global dominance. What I meant by not extracting "significant value" was a situation where no external empire can easily use the Americas as a springboard for global domination as they did OTL. Perhaps the nations there (either Native American or colonists from elsewhere) would operate independently from external powers. I was envisioning a situation where there American Nations mainly buy only from each other. The nations would do their own processing and mainly finished products would be sold to nations outside the Americas.
Good point about it being hard for all the nations to be insignificant. Perhaps we can go with
@Fabius Maximus said and have large isolationist power blocks cover the Americas. Large and powerful enough to resist interference from external powers but not inclined to contribute troops or resources to any external wars.
@Skallagrim , I like the idea of the religious revolution in the Americas. What might be the earliest we could get something like this? The earlier it happens the less powerful external empires might become off American resources.
@desmirelle , the Americas can be involved in external politics but it either is so small or lasts for such short periods that it doesn't boost the European empires to global dominance.
@sarahz ,
@Clandango and
@metalinvader665 . Both the revolting European colonies and powerful American Indian nations sound like fascinating routes to take. Might both be worth a separate timeline

If the nations decide to mainly trade among each other and sell mainly finished products outside how successful would these nations be?
If you colonise the Americas to the degree Spain did, you
have a springboard to global dominance, or at least to the degree Spain did. That means the wealth from the Andes, Mexico, and elsewhere fuels your campaigns in Europe to achieve dominance over the continent. Even if Spain didn't have Andean silver (via a surviving Inca), they'd still be pretty wealthy and powerful. And unless the Inca were permanently isolationist and anti-European like Japan/Korea were at once point, then they'd be leaking silver into the world economy since they'd be needing to buy all sorts of things from Europeans and maybe Asians.
It's definitely something which you'd need some sort of ideology to have happen, call it "Columbianism" (in the case of post-colonial nations), that promotes the development of the New World and its supremacy, and avoids trade with Europe as much as possible. Combine it with a Bolivarian Pan-Americanism sort of ideology. And there's plenty of opportunities for trade within the Americas, of course. But with such a pan-American/"Columbianist" spirit, it's hard to imagine how much you could splinter the continent(s) since there will evolve a natural tendency to avoid secession when trying to resolve disputes within nations. Not so much to avoid a government in Caracas seceeding from the government in Bogota, but maybe enough to prevent a government in Cartagena de Indias from seceeding from Bogota.
But how do you get a seemingly counterproductive ideology like Columbianism to develop? Maybe you do need a surviving Inca Empire. Maybe Spain nibble away at the edges a bit, but it still consists of modern Peru and Bolivia and bits of Ecuador and Chile, and managed to weather the storm of European colonisation by closing itself off. Although there's plenty of voices within Tawantinsuyu to modernise (think 19th century China), the very isolation of the Inca, it's relative success versus every other Indian group (ground beneath European heels or compared to the Inca "primitives" unfit of recognition), and it's prominence as a reminder of pre-Columbian civilisation end up being an inspiration to the rest of the Americas. We have to remember that even though there were violent indigenous Andean rebellions like Tupac Amaru and Tupac Katari in the late 18th century, the ruling class of the region a few decades later came up with an idea to crown a descendent of a Sapa Inca as king. A surviving Inca Empire, even if it's backwards and resembles the Qing at their worst, is going to have a lot of admirers. Hence the ideology of Columbianism might develop, and I guess we can assume a Columbian wank.
Nearly exactly same thing (independence movement and then rapid fission of states) has happened in OTL 19th century South America. It explains the huge disparity in development of South and North Americas in 20th century. The fragmentation could be much worse, especially for Argentina. Overall, fracturing of nations will delay development for may be one century.
Not just Argentina. Brazil could've fragmented much worse, and so could Gran Colombia and Mexico. Central America (which still could've added at least the Republic of Los Altos to the nations of the region) is a good example.
But it could produce a few more "Uruguay" type states, although aside from Buenos Aires province, Rio de Janeiro, and a state consisting of Santiago de Chile and Valparaiso, I'm not sure how many more opportunities for states like that could arise. By Uruguay-type state, I mean one which has a somewhat natural/easier path to following the history of Uruguay and thus creates a state which compared to at least OTL Latin America ranks high in economic indicators, lack of corruption, social indicators, etc. Uruguayan writer Eduardo Galeano described Uruguay as the Switzerland of Latin America, for instance. Essentially, more "city state with a large hinterland", since Uruguay is basically the city-state of Montevideo.
Of the ones I named, Buenos Aires would obviously have its own civil war to deal with (like Uruguay). After the first Chilean Civil War not long after independence, Chile was probably the most stable country in Latin America until the 1891 Civil War, so a Santiago-Valparaiso compact state could continue that and possibly avoid any later civil wars. Rio de Janeiro (maybe consisting of Rio de Janeiro State in nowadays Brazil?) may or may not have the Brazilian monarchy for stability.