I think if 99% of your hunting will be moose and deer, a .375 Flanged with a QD low powered scope would be the the way to go.

A .400 also with the option of a low powered scope would provide a little more assurance if hunting buffalo and elephant.

A .450 is in my opinion (limited as it is) is getting to be within the minimum of a TRUE dangerous game DR. IMO DG DRs START at the .450, another step up at the .500, and then serious DG DRs start at the .577 and above.

The medium bores such as .375 to sub-.450 do the job well 95% of the time, but lack the assurance of the .450+.

So a .450 with the option of scope mounts, shooting a 350 gr bullet for thin skinned game and a 480 gr for DG or larger game would also be an option. With the negative of more rifle weight and recoil when hunting moose and deer with it at home.

To sum up IMO:

.375 better for most of your hunting at home.

.450 better for the DG part.

.400 compromise.

All will work IMO.

I myself would like a modern .400 with QD scope for exactly the same purposes, hunting plains game in Africa, possibly with certain limitations, but also being a reasonable calibre for buffalo and elephant and the like. And also being able to be used at home for hunting medium game when I feel like it.