Why not have your cake and eat it too? Try the Beowulf 50 cal AE upper receiver for the AR 15. 50AE round, semi-auto, 7 rounds in a modified M16 magazine. Here's a link:
http://www.gunbroker.com/auction/ViewItem.asp?Item=19581021
BTW, I was being a little sarcastic, since the topic was wound size vs terminal velocity. You can have both in the 458. (and the 50AE, too!) You are right about the single shot. It is normally encountered in a four shot bolt action.
As far as home defense goes, it depends on how much shooting you expect the engagement to require. A .22 might require more than just a few shots to get a youthful thug, scared and full of adrenaline (or drugs) to go down and stay down.
Remember that recent home video footage taken outside a courthouse where a disgruntled client made a "final payment" to his least favorite lawyer using a small caliber hand gun (.22, .25, .32)? He emptied the gun into the man (can't recall if it was a revolver or a semiautomatic) from about two feet away. The shooter was firing from waist level, so it is hard know how many hits were actually scored. The one thing that didn't happen is that the victim didn't go down. He backpedaled away, held his hands in front of his body, cried for help, tried to hide behind a tree, etc. The shooter, frustrated, finally fled and was run down by a sheriff/bailiff; his girth being too ponderous to permit a true getaway effort.
Returning to the young, scared criminal in the dark, are you prepared to reload in the dark to make sure that he (or them) goes down? If you live in a isolated location where 15-20 shots fired in the dead of night would go unreported, you have some decisions to make, like 1) how to explain it to the police when ballistics analysis shows that the last six when into the dead guy AFTER he was on the ground, or 2) whether or not report it at all (and take care of the cleanup yourself). No. 2 is not such a good idea because there can always be a lookout or driver waiting outside. And he/she is going to go home and start talking about it and the next thing you know you're doing No.1 anyway. If you live in more populated areas, the police are probably going to be there pretty quick even if you didn't call them when the break-in/disturbance began.
So, if you have crossed the mental Rubicon and decided that you will shoot to protect yourself or your family members, you might as well choose a weapon whose first shot (and every shot thereafter) has the capacity to fatally wound/kill outright. It's just easier to 'splain it to the police if there was only one shot fired (in fear of your life before the police got there, of course) and the dead guy took it standing up (preferably delivered to the front of the upper body). Keep the story simple.
Since sight alignment and trigger squeeze can be just a little off when YOU are full of adrenaline and in the dark, the weapon of choice is a short barrel shotgun.
Personally, mine is a pump action deerslayer style 12 gauge with a magazine extender tube. I keep it loaded with a mix of 00 buckshot and 1" slugs (wound, kill, wound, kill, etc..). I have practiced getting it out and moving through my home with it in the dark (dry fire, of course). I have never had to get it out for real and hope I never will.