hahaha Joe I feel as though you must have had a really bad experience with one of these big calibres at some point in the past? I went from living and breathing the 375H&H like you do ( and I actually still do, absolutely love the 375H&H, my RSM is currently with my gunsmith getting a trigger job ) and then went all the way up to 500 Jeffery, I also came all the way back down to 9.3X62 (also now one of my favourite calibres) but now with all the calibres and rifles I have owned and hunted with I have settled at 450 Rigby and/or 470 NE for an open sighted big bore and 375H&H and/or 458 Lott for a powerful rifle with a low power scope (the longest shots I take when hunting big/dangerous game is around 120 yards).So let me offer some soldierly wisdom - Never stand when you can sit; never sit when you can lie down; never lie down when you can sleep. That British fellow Churchill even used the expression after a bit of campaigning in Natal, India, and the Sudan.
It is a very short logical step to applying the same same principle to a rifle the weight of sewer pipe, with accuracy we wouldn't tolerate in a cranky Model 1911, and the recoil of a baseball bat swung by Ty Cobb.
But as I say, if that is somewhere an aspiring African hunter wants to park his money - sure why not. I would simply suggest putting the first shot exactly where it needs to go with enough gun might be a more useful goal.
Having said all that for the most part I agree the 375's are probably the most versatile and easiest to place a good first shot with if all else such as rifle fit etc is good. But if you can shoot a big calibre well then I say why not, half the fun for me is practicing with big calibres and learning to shoot them well, I like the challenge.