My initial question was how a bullet with similar ballistics, but significantly different weights (a 140 grain .270 Winchester bullet traveling at 2,916 ft/s with 2,644 ft·lbf and a 300 grain .50 Beowulf bullet traveling at 1,870 ft/s with 2,330 ft·lbf) really truly differed.
As has been pointed out, the more aerodynamic spitzer of the .270 starts out at a higher velocity and retains it better over distance than a large, blunt pill like that of the .50 Beowulf
Another difference in the terminal performance between these two is directly a result of the velocity; The .270 (or any other high velocity rifle round) produces wounds far larger than the bullet diameter, while slower rounds (under ~2,000 FPS) do not create that kind of permanent crush cavity, and significant trauma is only evident in the tissue directly contacted by the bullet.
Penetration? All else being equal, lighter, faster bullets penetrate hard barriers better, but in live tissue, the heavier and slower bullet carries with it greater momentum, thus tend to penetrate flesh better. This is why dangerous game rifles are usually chabered in large bore cartridges. Close-in, a big, blunt .458" bullet will do much better against the thick-skinned, densly-built and very large species. But for a 400 yard shot on an 800 pound bull elk, the poor trajectory and rapid deceleration of these big bullets makes them a rather poor choice as compared to the common big game rounds like .270 Win, .30-06, 7mm mag, etc. That's not to say a .458 win mag won't kill an elk cleanly at 400+ yards, but it would be rather silly to tolerate the recoil and have an 8 foot hold-over.
Let's compare
7mm Rem Mag, 160 Gr. Accubond, 200 yard zero:
Velocity/ Energy:
Muzzle: 3,000 FPS/3,213 FPE
500 yards: 2,317 FPS/1,908 FPE
Max height above line of sight: 1.4"
Drop at 500 yards:
34.5"
Free recoil energy (7.5 lb rifle): 27 ft/lbs
.458 Win Mag, 500 gr. Banded solid RN, 200 yard zero:
Velocity/ Energy:
Muzzle: 2,100 FPS/4,945 FPE
500 yards: 1,233 FPS/1,686 FPE
Max height above line of sight: 4.1"
Drop at 500 yards:
96.4"
Free recoil energy (7.5 lb rifle): 72 ft/lbs