I have hunted plains game on several occasions in Africa. On some, I used a .308 Winchester. On others, a 280 AI. Both made clean kills at the ranges the animals were taken. Arguing which cartridge was better at killing those animals at those ranges is indeed splitting hairs.
But I have taken also a few of the larger animals with my .375 Ruger. While those animals were not any killed any deader, that cartridge does offer a much wider margin of error if the shot must be taken at difficult angles or if tracking a wounded animal would be unusually difficult or possibly dangerous. Choosing to shoot that cartridge in certain conditions is not, in my opinion, splitting hairs.
Define the parameters for the game you will be hunting and the conditions you will be hunting in. You will find a number of cartridges that will meet your requirements and choosing among them may well involve splitting hairs, but that's the beauty of having choices.