The 221 case itself is a great little package. Until I started seriously selling off my firearms about a year ago I had 5 221Fireballs and 3 17MachIV's. No doubt the 17's quickly replaced the 22's as my go-to choice on this case when I started shooting them many years ago, but they were all good.
In the 221FB, I still have my very early XP-100 (in a Fajen Victory stock and it is a really good shooter even with the factory 10" barrel), Just shipped the CZ 527 with exhibition wood a few weeks ago, and sold 3 TC Contender barrels over the last year... a 10" factory octagon and 2 custom Bullberry 12" stainless bulls (still have 2 of the M4's too, both NIB custom Bullberry Contender barrels -15" & 20"). So, I guess you could say I liked the case for both predator and varmint hunting - alot. I also had 5 22 Hornets and 3 17 Ackley Hornets, one 218 Bee and 2 17 Ackley Bee's, and this case does step it up over all of them a few notches.
I'm not sure what you mean by ease of reloading verses the Hornet. If you mean in finding a good load for, I never had any trouble finding them for any of my Hornets although I know some folks do, nor any problem finding them for anything I shot this case in either. The 221 is no different than loading for a 222/223 except for less powder.
L.