Hardest: 7 has the single hardest boss fight, but I think the hardest game overall (for me, I mean) is MM&B. I don't play it often enough to know it as well as I do the others. And Dynamo Man is a [sonic slicer].
Unless we're talking no pause-trick. In that case, there is no topping the original.
Easiest: Very close competition here between 3, X4, and Xtreme2. It's probably in no small part because I play the hell out of them. But I think I'll have to go with X4. Even when I was first learning that game, Sigma, Dragoon, and Double were about the only real trouble-makers. Learn to dance around them and you're set.