Sam Adams speaks truly when he says: "Physics doesn't change, nor the construction of the human body. What would have been very effective 70 years ago will still be effective."
We should always keep this in mind when analyzing any cartridge.
And Onslaught reminds us of a truth: "Don't get me wrong though, I'm all for a bigger round, but to say that the multiple hit issue is limited to the poodle shooter is not true. If it happens with the 7.62, then the same thing will most certainly happen with the 6.8, 6.5, or whatever."
I mentioned elsewhere that a G.I. on Guadalcanal complained he had to shoot a Banzai-charging Jap with six rounds of .30-06 from his M1 to drop him.
NEVER UNDERESTIMATE THE POWER OF ADRENALINE!
And we know from hunting that even if the heart is destroyed, it can take a while for the oxygen to "drain" from the system via blood loss and a "dead" animal can run quite a ways in a few seconds. Likewise, a mortally wounded enemy, a "dead man walking" can still squeeze off quite a few rounds before he drops, whether his heart was destroyed by a 5.56 or .50 cal.
So, in one sense, a 6.5 bullet is a 6.5 bullet. It's not suddenly magic because it's put into a military round. It's effects are well-understood from the hunting fields. But if terminal effects are somewhat unpredictable because human reactions to being shot are unpredictable, there are some things we can predict.
We can predict ballistics and trajectories, which help in actually hitting the target. We can predict penetration potential, based on physics. And finally, all else being equal, a bigger bullet will create more permanent damage, leading to greater blood loss and quicker death.
Even if there's anecdotal evidence that bullet size can't always predict incapacitation, I'm sure that if you studied it statistically, the .50 cal, over the long haul, leads to faster incapacitation than the 5.56.
Conclusion? For shoulder arms, get the biggest bullet that has no more recoil than the average recruit can handle. Get the biggest bullet that has the trajectory you desire. Get the biggest bullet that meets your penetration specifications. Get the biggest bullet that fits in the most compact package to get your best ammo load weight and weapon size.
Cartridge design is always an exercise in compromises, but my theory is always get the biggest bullet you can, within your design constraints. It's not going to guarantee 100% one-shot kills, but the odds will be in your favor.
John