Shot placement, shot placement, shot placement.
Secondarily, bullet construction and performance.
I lost count some where upward of 300, and have lost several dozen. Those lost were mostly due to misplacement of a bullet that didn't perform as expected (inadequate expansion).
Can't say I've lost more than half a dozen due to excessive expansion, but those that I did were mostly with .243's and 100gr bullets... at close range.
but, I've had a few inexplicable drop-deads with shot placement that shouldn't have done so.... Notably one with a 150gr FNGC bullet that passed broadside approximately 1" under the spine, but deer dropped dead with little blood loss...
I've killed some with a single shot from a .22lr to the head... Had a couple run off with real bad headaches too.
I've heard that it even makes a difference if the heart is in compression or between beats...
I will still shoot for center of chest on longer shots, and spine where range and conditions permit more exact placement. Only in instances of very close range and controlled circumstances will I take a head shot. Had too many "ugly" results requiring less than optimum followup shots to "fix" a botched first shot to the head.
Sometimes there just isn't a good answer.
Nature is dynamic.