I've shot deer from 5 yards to 500, standing and often, walking fast, running, etc. The only times I ever felt under-gunned was when I used a shotgun or iron-sighted rifle.
Once, I planned to hunt in tight wooded cover, so had a semi-auto shotgun with slugs and buckshot. We broke out on a powerline and suddenly saw a nice buck walking along the other edge, about 150 yards away. The shotgun didn't have sights, just a bead, but I think it's really too far to shoot at a moving deer with a slug. Some will argue, but I decided to not shoot.
Another time, I was hunting with a Marlin 336, .35 Rem and had the same situation, but the range was closer to 200 yards. Didn't shoot again.
Since then, I've hunted with .243 Win, .30-06, and .270 Win and felt confident that, as the rifle is sighted in, using the rule of 3's, the bullet will hit within 3 inches of the crosshairs of my 3-9X scope from the muzzle to 250 yards with any of the three. Beyond that, the .270 Win, will do the same out to 300 yards with predictable holdover beyond (but only if those distances are known within 25+/- yards).
I personally feel confident in my ability to shoot well into the deer's kill zone offhand to at least 200 yards, but don't want to worry about holdover of, say, a .30-30 or .35 Rem at distances beyond 100 yards. The .243 Win is the minimum cartridge that gives me that needed ballistic confidence. I use 80 grain Hornady GMX handloads that don't lose more than 3 grains of weight on impact, yet fully expand and penetrate deeply. Factory 100 grain bullets are the norm for most hunters and they hit very hard.