I have used 270 gn TSXs for the past 10+ years in my 375 H&H and have taken dozens of animals with it. I find it gives a good combination of penetration and velocity for 300 + mtrs and have never had to track a single animal shot with this combo. Every single animal has succumbed almost instantly with the exception of a giraffe, which lasted about a minute, maybe two and took a second shot. They are incredibly tough animals. I have taken everything from impala and puku up to hippo, croc and giraffe with this rifle and load and have recovered many bullets. Their final form has varied from perfection with all 4 petals folded back and intact to no petals remaining and just a cylindrical piece of copper looking like a miniature 45 gal drum. I have several of the latter but to be fair all encountered exceptionally hard and large bones like the spine of a lion and bongo.
For my 375 Wby I have had Marshal @ Matrix make me some 285 gn spritzer RBTs to try out, but have not tried them on game yet, and also some 325s for my 378 Wby which I again have not tried out yet. My son has had great success with 260 ABs in his 375 Ruger and found it to shoot flatter than a 30-06 165 gn and arrive with great authority and virtually instant kills. He has made a couple 400+ mtr shots with his on a kudu and some other critter in RSA and impressed the hell out of his PH.
The reality is that virtually any appropriate bullet in the various 375s (exclude the 375 Win) will very effectively handle all NA game with great aplomb, almost irrespective of animal presentation or orientation to the shot. It is truly an outstanding do most everything caliber with any appropriate bullet, even the 235 gn Speer HC bullet does an amazing job at H&H or Ruger velocities.
Just a bit of trivia for ya, Kynoch, when they originally worked up loads for the 375 H&H for Holland and Holland were tasked with making the 235 gn @ 2900 fps, the 270 gn @ 2700 fps and the 300 gn @ 2500 fps all shoot to the same point of impact at 100 mtrs. Which they did and can still be done with this cartridge today with a little load work, and one can add a fair bit of velocity to each weight with the newer powders.