Thanks for everyone's input.
I don't reload, so I'm stuck with factory ammo.
I have a .204 and .243 for varmints and small to medium game. Plus I have a .35 Whelen for medium to large game. But the .35 is like shooting artillery and lacks range beyond 250 yards. So I'm looking for something capable of taking deer or large game at 300-600 yards.
I've considered the 25-06, but since I have a 243, I figured it was already a close match to the .25 caliber.
The calibers I'm now considering is a .270, .300 win mag, or a .308. The .308 has lots of ammo and is used in competition. But that's because it's consistent and (if you know you the distance) you can calculate bullet drop. But it's slower and doesn't carry as much energy to the target as the faster bullets. Which is fine for punching paper, or against thin skinned game. But against larger, heavy skinned animals, it may not be the best choice.
The .270 seems like a popular flat-shooting favorite, has more ammo than the 25-06, and offers a broader range of bullets, some of which are heavier than the 25-06 and should provide more energy at long range. So this may be a good bridge between my .243 and .35 Whelen. Plus, the .270 is extremely versatile and can be used almost anywhere, and against almost any game in the world.
The .300 win mag carries even more energy than the others, but I wonder if it may be too much gun for most game and shooting conditions in Missouri. It would probably work great out west, but I'm not sure if it's the best choice for here.
Any thoughts?