A .25 caliber bullet with an impact velocity in excess of 2000 fps is a reasonable minimum for North American big game, meaning that a .25/06 is useful well beyond the range at which big game is typically shot. Having said that, bullet choice for high velocity small bores is far more critical than it is for larger bore rifles with less velocity and heavier bullets. At one time I would have said that the 120 gr bullet should be the minimum for big game with a .25, in that the .25/06 performs much like a .270; but the 100 gr TSX requires that statement to be reconsidered. At the risk of sounding inconsistent (I don't like the 100 gr .243 for big game) the .25/06 is ahead in terms of velocity and there is no .243/100 gr TSX. Therefore I believe the .25/06 with a premium big game bullet meets the requirement of having a reasonable expectation of killing a big game animal with a single shot from any angle within the range limitations of cartridge and shooter.
I believe we should get as much versatility as we can from our rifles. If moose, elk, or big bears were to be the normal targets for this rifle I would step up to a 6.5, a .270 or a .30/06 and load heavy bullets, but if deer, caribou, black bear, or sheep were the usual targets, and moose were only hunted occasionally; the .25/06 would remain a fine choice.