I live in Northern Nv, and we have much opportunity for longish shots.
Given that, I have started using a Ruger No 1 chambered in 6mm Rem.(a .243 would be the same) and don't feel like I have given up a thing to my 300 mags on mule deer or antelope.
I might be a little more concerned if I were to use a "mid velocity" round as many have suggested.
My vote goes to the 6mm-243 with 100 gr bullets.