Empty Quiver...Your thoughts about what calibers they carried is wrong...
Daniel Boone and David Crockett didn't carry .36 caliber flintlocks...And a 22-250 is more powerful than a .50 caliber round ball in front of a .490 ball in front of 100grs FFF Goex at 100 yards...
The American Longrifle started being developed during the first half of the 1700s...It was developed by German gunsmiths that were use to making Jeagers of .54-62 caliber or so...Many of the flintlocks during the American Revolution were .50 caliber or larger...This is the type weapon Daniel Boone carried into Kentucky when he first went there in 1769...
By the time David Crockett was in the Alamo (1836) calibers in the eastern US had gotten smaller because the deer population was decimated by market hunting...David's favorite rifle "Betsy" was actually around .48 caliber...But many rifles from that period and later were .36-.40 calibers...The stock design changed as well and went from the wide, flat butt of a Lancaster to the curved, narrow butt plate of a east Tennessee or western Carolina gun...
So all the Hawken boys did was go back to larger calibers from the Revolution and instead of swamped barrels they went to heavier barrels with a taper for heavier powder charges...
But to your original question, yes they did in fact discuss larger vs smaller balls for game...I can't remember who it was but I have seen period documentation that said something to the effect that while some hunters prefer smaller bores as they require less powder and lead others prefer the larger bores and the certainty of quick death that follow...
I've killed deer with .40, .45 and .54 caliber flintlocks and round balls...I prefer a .54, it puts them down a bit quicker and leaves a better blood trail...But maybe what is more important is I have had a large black bear within 35 yards of me and a .45 caliber flintlock in my hands...I made the decision to move up to a .54 at that time.....
With modern rifles...During the '70s, I killed 50 or so whitetails with a 22-250...In 1980 I moved up to a .243 and have used it ever since with no complaints...This was before the current selection of .22 caliber bullets...While I know .22 centerfires will kill deer, I wouldn't go out and buy one just to deer hunt with...