I'm wondering how a round like the .376 Steyr would compare with the .375 H&H, RUM, Weatherby or .378 Weatherby in effectiveness on game. Is there a marked difference that the extra velocity will provide in knock down effect or does the extra velocity add just a little more range?

I think the performance will depend on the bullet you use. It is probably misleading to qualify any .375 caliber bullet in terms of "knock down" effect. Since I don't shoot a .376 Steyr I would reply that the standard rules apply: 1)on a non-premium bullet (read a non-bonded soft point) the increased velocity will more likely just result in bullet break up and therefore be less effective than at a slower velocity at shorter ranges, 2) a premium bonded bullet will be more prone to exit the animal at shorter ranges, 3) a round nose solid will most likely just run right through the animal at shorter ranges whereas a flat nose solid may penetrate less if the terminal velocity is over 2400 fps. So I think you are right, any muzzle velocity over 2400 fps is more about increasing the effective range than increasing any "knock down" effect. The bullet will do the right thing a little farther out and you may get a slight benefit in point blank trajectory. The downside is you may get reduced bullet performance at close ranges.

Winks' response about right, only a FN solid will propably penetrate more, not less, at most velocities (over or under 2400 ft/sec). The extra energy of the faster rounds does not make a big differeance IMO, if bullet weight and quality are the same. A faster soft nose might even penetrate less than the slower one. I would steer clear from the faster rounds, but go with what YOU like.

I think the principles I am talking about hold true for most of the larger calibers and most of the bullets you will encounter. There are some exceptions with certain types of bullets, at least that is what I have been led to believe and what certain knowledgeable bullet makers say (such as NorthFork). But it all depends on where you are going to hunt I think. If most of your hunting is to be done in conditions where the majority of shots will be over 200 yards then the higher velocity rifles have some appeal. Of course they have greater recoil, probably need to be made heavier to be tolerable to shoot, have increased muzzle blast and perform less well at shorter ranges than the slower calibers. I have never shot anything over 160 yards because I have yet to hunt in the open conditions which might require it.

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I am in the process of testing the 375/444 (aka 375jdj) from a double rifle at all species of African game. The first loading was Speer 235 gr at 2350fps. Worked great on larger plains game esp. if bone was hit. But acted like a solid on smaller species or if no bone was hit. This season I am going to shoot Nosler Accubonds at around the same MV on large PG. If you want a bullet to expand, remember that almost all 375 cal bullets are designed to work in the H&H, so if you are shooting slower, avoid the tougher bullets and use regular cup and core bullets, or those made for the 375 Winchester (Barnes Traditionals).