I believe in keeping your calibers simple. I own 22 guns now and all of them are 45/70, 357, 22LR or 12ga. I figure its easier to stock up on 4 kinds of ammo than it is 20 kinds of ammo.
Look at it this way. If there every is a major collapse and one of your guns breaks or is stolen you ammo will still work in the other gun.
Shot placement is everything! I would rather take a round of 50BMG to the foot than a 22short to the base of the skull.
all 26 of my guns are 45/70 govt, 357 mag, 22 or 12 ga... I believe in keeping it simple. Wish my wife did as well...