Berzerker
Deity
I think that you overstate the extent to which hunter-gatherers were battling mammoths or whatever. Humans mostly hunt birds and small mammals, and will mostly seem to have done so through trapping or extended pursuits. Dramatic scenes of ambushing mammoths are very romantic, but not typical.
And apparently it was the climate change associated with the Younger Dryas that wiped out much of the mega fauna, not us... The environmental disaster took a toll on the Clovis peoples too.
Most of the really nasty communicable diseases, the ones that merit the status of "plagues", originated in domesticated animals. This is why many of them were absent in the world outside of Africa-Eurasia, even in the dense urban cultures of Mesoamerica and the Andes. You can't get Bubonic plague without cattle.
Is that why new world peoples were so vulnerable to old world diseases?