I understand kinetic energy, it's kinda baked into my career, but it gives almost no prediction to results on target. KE doesn't describe how the bullet transfers its energy to living tissue, only what it's doing at any given point in the direction vector of its trajectory.
A magnum caliber with a mono bullet will have far more kinetic energy than a moderate caliber with any bullet. But the level of damage to vital organs is often inverted if you pick a good expanding/fragmenting bullet for said smaller caliber. That's because what the bullet does once it enters tissue matters far more for rapid lethality.
This is why Q and Kevin B, who have designed cartridges around monolithic bullets, advocate for spinning them as fast as possible without the bullets coming apart. Because the standard wound channel of a mono bullet is pretty abysmal, whereas if you ramp up the RPMs it has an immediate and drastic effect on permanent wound cavity. You're displacing far more tissue with a centrifugal energy that is off-axis to the direction of travel.
The same thing happens with a fragmenting or tumbling round, where massive tissue damage is caused by "pieces" of the bullet breaking off and continuing on their own skewed trajectory through tissue. You also gain the advantage of transferring far more of that beloved KE to the animal, where a much "tougher" bullet, or a solid, will retain (i.e. waste) that energy upon exiting the animal, therefore causing far less trauma.
Most hunters would be better served with a smaller caliber and better bullet vs maximizing their KE with a magnum unnecessarily. Because you're right, you can shoot a bullet that does far more tissue damage than desirable when you get into magnums. So imagine taking a bullet design that is maximized for lethality and putting it into a smaller cartridge that is easier to shoot, but has far less KE on paper.
I agree that what we want with expanding bullets is maximum energy transfer. The bullet must decelerate as much as possible between entry and exit, preferably in the space from after it has penetrated skin and exterior muscle/bone to within the vitals to when it leaves the vitals and hits that exterior bone/muscle/skin layer. That should cause the most tissue damage, quickly. Too expansive or non-expansive is not good. We want the Goldilocks bullet... just right. That's where bullet selection, influenced by the game, the cartridge, and the anticipated ranges comes in.
Fast barrel twist/spin rate leads to bullet tumbling and thus more rapid energy transfer with long for caliber bullets due to the larger surface area presented by a tumbling bullet... these bullets aren't over-stabilized but merely adequately stabilized, and have the center of balance behind the midpoint of the bullet... the only reason they fly point forward is because of spin.
Given two bullets with identical terminal performance, the one with higher kinetic energy at impact will do more damage. Will it kill more quickly? Yes, but absent a significant difference in energy there won't be a significant difference in speed of killing. Of course this depends on the critter; the difference in game response between a hit by a .243 through the lungs and the same hit with a .338 Win Mag is generally an observable difference in that the game drops quicker, doesn't run as far or at all, with the more powerful cartridge. My admitted guess as to the cause is because while both provide sufficient internal trauma/wounding, more kinetic energy causes more disruption to the CNS... akin to a moderate punch to the gut versus a hard one... and the effect is more pronounced on deer than on elk.
This is a fascinating conversation for me. I'd love to see someone... ammo manufacturer, bullet company... undertake a study on this. If it were my study I'd pick four distinct calibers, say .243, 6.5/.264 or .270, .308, and .338, and try to find bullets for each caliber that would perform similarly in terms of percentage of energy transfer (not in terms of performance) at the same velocity. I'd do this by testing them at a common velocity on maybe steers or axis deer, to get a baseline/benchmark. Then, I'd load sets of ammo (all calibers at the same velocity) for different velocities representing expected velocities from 50 to 400 yards for standard and magnum velocity cartridges, at 50 yard increments (so maybe 9 to 10 overall 'sets'). I would want to shoot 10 animals per cartridge at each range, in the same exact spot (broadside, mid-chest, 4" behind the front leg, to go side-to-side through the front chest of the animal). I'd like to rig up some way of catching the bullet on the other side and maybe placing a radar chronograph to get exit velocities, and chronograph every load from the bench/rifle. Of course, since these are domestic animals they could be staked or roped and the rifle would be in a rest to ensure maximum consistency of shots. Each animal would be shot once and then autopsied... any animal that didn't die within X seconds would be euthanized. The time from impact to collapse and impact to death would be recorded along with hit attributes (was bone struck, damage volume to organs, what organs were struck, etc.). That would require 3,200 rounds fired at a minimum. Likely impossible today, at least in the US. Maybe in South America or Africa though, and likely cost-prohibitive for most companies (likely well over $200K). The data collected would be sufficient to let us draw some firm conclusions and to establish a baseline database for further testing.
What would we learn? Minimum energy thresholds (for that size of critter) for effective one-shot kills, energy thresholds for rapid/instant kills without CNS hits (if there is one), the difference in lethality for different calibers at different velocities/energies, should there be a minimum caliber, bullet weight, and velocity for ethical big game hunting, maximum effective range for quick lethality for specific calibers/velocities... and that database could be grown over time with different bullet types, different shot placement scenarios, etc.
Now I'll argue against myself by saying that we likely know enough to make informed decisions without having to know everything. We know that a .243 on up with an expanding bullet designed for big game will, on a broadside shot through the chest cavity and hitting the lungs, kill a deer out to 400 yards and an elk out to 300 yards quickly enough to qualify as a valid/ethical choice, that stepping this up to .264-.284 calibers gives us at least an extra 150 yards, going up to .308 gives us 100 more yards, and going up to .338 gives us another 100 yards. The effective ranges for each caliber are longer, but the ranges above are certain and sufficient to make valid decisions on hunting calibers. So, maybe, we don't need to run a large testing program.