243Win/375H&H: The ultimate Two-Gun/Do-Everything combination
Hmmmm, not a half-bad l'il plan - can't argue with that. In fact, I may agree exactly or just almost. Of course, no right or wrong answer. I "cover" worldwide large game hunting (now), at least in theory, with just 5 rifles. Actually just 4 since the 5th is really a "wife/backup" hunter. This is WAY down from the old days - even just a year ago, it would have been at least 6 or 7. Now if you add varminters, general purpose rimfires, and combo longguns, the number goes way up quickly (triples from 4), but the varminters double as fun target guns, as do some of the rimfires. But for any largish edible game, it's *just* four rifles now. Maaaay cut that to 3, but I doubt it. If anything, I'm more likely to add one (get back in the .45-70 game with an 1895 SBL) than to cut one out and go to just 3.
I'm generally very happy with simplifying, and will continue to do so to some extent. Not counting bows and edged weapons, I finally pared down enough to achieve the 30-or-less weapon threshold (guns & muzzleloaders) - actually only 26, but four more guns I want. But since I enjoy bowhunting more, I have a lot more bows now. Used to have 1 or 2; now it's 5 and counting, between bows & crossbows. It makes sense to keep going in that direction (more bows; fewer rifles), since the season is longer, practice is cheaper, and I enjoy it more than rifle hunting. I will probably settle near the 25 guns & muzzleloaders / 8 bows marks. But the guns include defensive handguns, shotguns, and carbines. Obviously, the goal here is to hunt more, and collect/store/insure/maintain less.
Also, if you don't know, there are many reasonably-priced turnbolts for sale nowadays in .375 HH mag - if you keep checking gunbroker, armslist, etc., you can occasionally find a CZ 550 for sub-$900, which is an excellent rifle. Sub-$800 possibly even. And these are typically in excellent condition (not fired much.
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Back to the original question: Really, IMO, what it comes down to is this: If you don't reload, you want a .270 win or a .30-'06. (.270 win if mostly plains / desert / loooong range, or .30-'06 if not mostly plains/desert).
If you reload, then it's wide open. If you have a lot of money to replace barrels and feed the rifle, why not get a laser like a .270 WSM or a 26 Nosler? But lots of options for the more padded wallet, and/or reloader, including the same "big two" mentioned above (.270 & .30-'06). Whatever butters your bread. To me, .260 rem or 6.5x55, and .280 rem are where it's at for North America, if you want to go bigger than .243 win. But it's hard to go wrong with any mainstream or semi-mainstream choice in a 6.5 or 7mm - as well as *most* .30 cals - .300 WSM is a good/ interesting choice if you want a lot of downrange energy (like plains elk at 400 yards on a regular basis, let's say).