Best what? Highest velocity potential, lowest ES potential, accuracy, chance of actually cooking off when struck by the firing pin?
I am a competitive1000-yard benchrester that uniforms primer pockets and seats all primers by hand for over-travel to obtain consistent ignition. The 250's I tried in various configurations of Norma brass had a misfire rate on the order of 1 in 50. Have no definitive technical reason why. (replacing a firing pin spring had no effect) The Ballistic Gods may have simply given me the "stink eye". I've never had a misfire with a 215, 215M, 210, 210M or BR-2 using the same reloading methodology.
I am primarily concerned with accuracy, regardless of target or hunting loads. The resultant velocity is what it is. My accuracy criterion for non-dangerous, big game hunting loads is 3 shots less than 3/4 inches (19 mm), on centers, at 200 yards (183 m), shot from a bench with a bipod as a front rest. With the 375 H&H case, I have comfortably achieved that criterion with BR-2's using RL 17 pushing a 270 Speer @ 2780 fps (847 mps) and H 4895 pushing a 300 SGK @ 2615 fps (797 mps). Both from a 24-inch (61 cm) barrel. No delayed ignition with the accompanying "snap, crackle, and pop" at temperatures as low as 40 F (4 C).
Each system is unique, so no powder charges or seating depths for the above loads will be furnished.
When components were available and "cheap", you could tinker with primers and a chrono to do applied and effective "mad science" to figure out "best" on your terms. Tough to do these days. One thing is for sure: my personal experience with the 250's I tried eliminates them from consideration for use in a personal dangerous game load.
I hope the above helps in making a strategic plan of action/decision.