The kill zone is the same size at 300 yards as 100....it's just harder to hit! :wink:
Seriously, if you are not 100% confident in shooting that far than DON'T do it. Even with my flat-shooting setup I won't take a shot that looks over 150 yards without laser-verifying the range first...and I'll range anything that looks 100 if I have time, just to make sure. I have seem too many people offhand and "hold over" at deer. Long shots take skill, time, and patience. And yes, you basically need to have a "bench setup", like a good bipod or shooting sticks, to make the shot.
There are currently 2 good light bullets that have 300 yard potential...the 200 gr Shockwave and 195 gr DC. They are the two highest BC ML bullets I've found. They make a 175gr DC, but it has a lower BC so you don't gain anything at long range from the slight velocity increase. There are a number of heavier bullets good to that range too...the 250gr Shockwave and all of the DC bullets in .40 caliber. But they are going to drop more, and due to the lower BC most of them won't really deliver that much more energy, either.
Precision Rifle has a lot of good, high BC bullets, but I've never gotten one over 2000 FPS and maintained accuracy. They are pure lead so I think they begin to deform (though the owner will claim you can get 2300 fps no problem, I have never known someone to do this). If you can drive a heavier one, like the 240gr DC, to 2000 fps, you will have a great deer killer. I'm going to try that one yet just didn't have time before the season. But since you can drive the 250 gr Shockwave to higher velocities, you might deliver more energy with it.
I don't think there is a huge difference in attainable velocity between the .45 and the .50 anymore. This would have been the case with the 195gr DC, but the available double-saboting system has pretty much solved this. The .50 leaves you with a much better bullet selection.