I think the overwhelming issue is and greatest tragedy was that is wasn't European military might, technological or cultural advantages, or anything inherent in the Europeans besides the tiny creatures they brought with them.
Smallpox in relation to the European conquest was like a flaming sword shattering all resistance and possible resistance in its path leaving the continent open for European settlement.
Unintentionally by making the trip the Europeans unleashed probably the most successful biological warfare campaign in human history. Far more natives died coughing of smallpox, and other diseases than died at the hands of European rifles, horses, and swords.
In some places the Amerindians put up admirable resistance-the chichimeca for example fought the Spanish for forty years and could not be subdued militarily, a Mayan city state held out until 1693 or something, the American Indians fought until the turn of the 20th century, and the pampas Indians fought contemporaneously to them for a long long time.
The natives quite simply without biological immunity could not resist European expansion-that cost them manpower, leadership, their very physical and social and psychological strength was shattered by a weapon the Europeans carried over but themselves did not understand.
If some ASB gave them immunity to smallpox, malaria, and the other myriad diseases they encountered I believe the Americas would remain majority Amerindian to this day.
Or if said ASB froze time for six thousand years in the old world-allowing the Indians a longer chance to play catch up. Because the Europeans did have a technological advantage that only grew over time. The Indians needed thousands of years to reach European levels of technology. Delaying colonization by a century or two would not have changed the fundamental outcome.
Even if the Amerindians say around 1200 AD got access to pigs and chickens-improving their diet and introducing the pathogens-it would not have saved them perhaps bought them more time but it would not have saved them. The Tarascans, Inca, Aztec, and Huastec starting the transition to bronze would not have helped them-perhaps increased European casualties slightly but even if you delay colonization for a few centuries allowing some of the Indians on the verge of transitioning to bronze to reach that point-it would have only delayed the inevitable.
Perhaps a more diverse gene pool or earlier arrival and settlement by tens of thousands of years would have evened the gap.
Honestly the outcome of the European arrival was foregone barring divine, extraterrestrial, or ASB intervention.
How about if these diseases, such as smallpox, found their way to the Americas via a trans-pacific trade route far earlier after they emerged, in a similar time-frame or shortly after their arrival in Japan? Biological immunity can be acquired the hard way; it just requires time for the population to rebound from the epidemics. No ASBs required, any more than they were required for the Japanese to survive contact with the Europeans. IMHO, the easiest way to have Native American civilizations which are on a par with those of the Old World, is to have at least one which spans both continents, and which essentially IS a part of the Old World, to a similar degree that the civilizations of Japan, the Philippines, and the Indonesian archipelago were Old World civilizations. The best candidate for this is probably an ATL variant of the Haida in my opinion; and an early establishment of the Maritime Fur Trade would also see significant migrant transfusions in the same way that establishing trade links with China did in Japan and across Maritime South-East Asia, which would serve to increase the size of their gene pool and boost their biological immunity levels in much the same manner as it did for the Yayoi Japanese. Not to mention that they're located pretty much exactly where you'd most want to be, in the Americas, to have the best chance of holding out against the Europeans' conquest- essentially, up in the far north-western corner of the Americas, spanning the Bering Strait, they'd be last on the menu, and thus the candidate with the most time to develop and to counter the European threat. Especially if they maintain control over Kamchatka Krai and Chutotka by either averting the split with, or re-assilimilating, the Koryaks and Chukchis, and manage to hold the Russians at bay.
Also worth mentioning- OTL's Thule people are/were a migrant group of colonial settlers who originated in this same region of Coastal Alaska, initially expanding westwards and southwards to the Aleutian Islands between 900 and 1100CE, before suddenly deciding to end their expansion in that direction, abandoning the Bering Strait, and turning back to expand in a north-easterly direction instead, where they displaced the Dorset culture and became the progenitors of the Inuits. And according to the Norse accounts of the Skraelings upon their arrival in Greenland, there wasn't that big a gap between them- the Thule had already entered the Iron Age in the 8th century CE, were the first (and only) Native American civilization who developed ironworking, and had already been smelting copper long before that. So then, what if the Thule expansion hadn't reversed its course to focus all of its efforts upon colonizing the Beaufort Sea, the Canadian archipelago and Greenland? What if the Thule had consolidated its control over the Bering Sea instead (or as well), and continued its colonial expansion south-westwards, all the way along the Kuril Islands from the Kamchatka Peninsula, until it reaches Hokkaido, in a similar time frame to when it reached Greenland IOTL (circa 1300CE)? In doing so, through contact and trade with Japanese, Koreans, Dauri and Chinese, they could easily pick up more advanced technologies, as well as domesticates like pigs, horses and cows; and as perhaps the most invasion-proofed region in the world, they'd stand a much better chance of holding out against the Europeans into the modern post-colonial era. And just like Greenland IOTL, the entirety of the territories under their control- Alaska, along with the Kamchatka Peninsula, British Columbia, the Kuril Islands and perhaps even Hokkaido- could all plausibly be majority 'Inuit', majority Native American, by the present day.
