Well, I've seen a .22-250 do some amazing work on big game (buffalo, brumby, camel), and I've also seen it struggle, which generally isn't a nice thing to see. A wild man I know has shot many buffalo with a .243 successfully, but, and I hate to say it, he has also lost quite a few. The reality is the two calibres I just mentioned really are kangaroo culling rounds. What is possible isn't always what is best, and as all bullets lose steam downrange, more grains is dependable as ever.