Those boolits work and velocities are just fine. My biggest problems have been too hard and too fast. I tried WFN instead of my WLN in the 45-70 and it made no difference, 200 yards to recovery. At the right velocities for the alloy the WFN has an edge but can be worse if shot too fast without expansion because the wave from the nose is wider.
Most of what I surmise is from just thinking about it at my bench after seeing the insides of deer. I have to leave out very large animals because I don't know. Big and tough animals might let the boolit work even if hard. It is the apples and oranges thing.
It is true you don't want to download H110 or 296 (Same powder) too much but starting book loads are fine. The only caliber to be careful with is the .454 because of the primer. I use 296 because it has made the most accurate loads. It has less instant thump on a boolit then Unique. 296 will not spike pressure suddenly if you go over max a little. I use 296 in the .44, .45, .475 and .500 JRH but the 45-70 uses 4759 because of case size.
I tried the 4227's in the .44 and got good accuracy but gun heat makes it go crazy fast but it worked superb in the .357 max. Something about the .44 so I stay away from it.
2400 can spike but it is good powder.
Notice I use a Fed 150 in the .44 and .45 Colt but go to the 155 for the .475 and up, even the 45-70. Don't use a mag primer with 2400 or Unique. You don't need it with 296 in the .44 either. Mag primers triple groups for me. The WW primer will work in the .45 Colt.
Air cooled is OK, I just get fliers but they seem to go away if I anneal the GC's. PB needs harder so I water drop.
The Keith boolits are good killers but it is the meplat, not the shoulder, the shoulder does not touch anything in an animal unless very slow.
The Lee 310 is a super boolit for deer. I use 21.5 gr of 296 and a Fed 150 primer. Velocity is about 1316 fps from my long barrel and 100 yards is nothing for the gun. The 265 RD with 22 gr of 296 is deadly with Felix lube, I hate Alox.
My old Vaquero .45 with 320 and 335 gr boolits at 1160 fps puts a hurt on deer. I use 21.5 gr of 296 with both. Don't use that in the new guns. Ruger should keep making both sizes instead of bowing to CA shooters. They could double their profits.