I guess it depends on several things ? What type varmit/predator hunting ? How far ? and how much you shoot in a day? If I were shooting a whole lot say 100+ rds a day @ ground squirrels or P-dogs, it would be any good 22/6mm class rifle depending on range, for long range squirrels @ 400 to 500 yds my nod goes to a 243 or 6mm. A hot 243's will shoot a 55/60 gr bullet @ 3800-4000 fps, really out shining the 22-250 at really long range, nothing wrong with a 22-250 great cal. If I were shooting @ 300 yds or less any 222/223 is great. A good friend of mine uses an old savage 24 over/under 12 ga/223 combo gun and when calling howlers or fox in very heavy cover a full load of # 4's puts them down and the 223 for long shots. Lately I have been using an ar-15 with 5 rd mags of course, for howlers the very fast follow-up shots is really nice and great for multiple targets. We have Mtn Lions , wolves, and bears in our area so when I go out calling coyotes and fox in their territory I usually take a 270 or 308 just to be on the safe side. Never shot one, but have called in several, just sat there and watched them, very cool one of these day's I will dump one. Wolves in our area are protected so they are off-limits. One day last yr my friend of mine and I were scouting for elk a accidently spooked a Mt lion that was sitting in the front door of an old abandoned cowboy line shack, I thought he was full of him-self so I left my rifle in the truck, big mistake, I went to the open door and found otherwise, cat was really ticked off, backed away very slowly with the hair on the back of my neck standing, we just let him go. Now I carry a 10mm colt auto max loads just in case. This is not the first time this has happened, 3 bear encounters in 5 yrs with family members has taught me a good lesson, be prepared, predators are just that, predators you sometimes just don't know what they may do. A good 243 is a nice way to go for all around predator's cartridge, it wouldn't be my first choice in bear country, that's why I carry a 270 or 308.