I've had .22-250s for years and loved the round. The problems with it are few, but frustrating. If you hunt grassy pastures or hayfields and miss a varmint, it's very difficult to spot the bullet strike, compared with larger calibers without super-frangible bullets. We started hunting woodchucks and crows with .30-06s and almost always could see where we were hitting. (Unfortunately, bullets ricocheted quite a bit, so we needed to be VERY sure of backgrounds.)
The other thing we noticed with the .22 centerfires is wind deflection. Wind is a big problem during spring chuck season in Maine. The .243 Win seems to buck wind much better with 85-90 grain bullets. I use one for both chucks and coyotes and love it, but wouldn't want to shoot one all day at prairie dogs.