I have always had some type of 375 on each safari. Most of the times I find it in my hands and use it in place of a planned to use heavier more appropriate caliber rifle.
So I have stopped fighting it and that will propably be my heavy from now on. I can't imagine me hunting anything above a buffalo from here on out. Some of my trips will be trips will probably be family driven affairs so I imagine heavy helping of plains game will be in order. Some will be to just enjoy Africa.
So now I have bolts, single shots, and doubles in 375 caliber rifles that I have decided will be my main rifle. I have to admit that now that I have added a double in 375 caliber that this has really gotten me excited to go back hopefully next summer. I have used the 375 solid and a lot of small animals and love it. Now with a soft and solid ready at the go without needing to work a bolt to expel a soft for a solid has me quite excited.
The beauty of the 375 is that it pairs with about anything. I have been using it with the 308 Winchester lately and for me does well
While a rifle in 375 would be a great one rifle gun I know I could never take just one as I am a gun nut but I could see a day where a double rifle in a smaller takedown case would allow a simpler experience on a safari and I might look to do that type of hunt.

So what is your one rifle or cartridge that gets you worked up for Africa or does the rifle matter to your experience?
For me the rifle is a big part of the experience.