It's a shame that we even have to discuss this. It is a shame that we live in a society that has to protect law abiding citizens (castle laws) who defend themselves. You should use the biggest caliber that you feel comfortable and competent to use in light of the tactical situation you may face (are their people in adjoining rooms, how close are the neighbors houses, etc.).
You should develop a home defense plan based on those tactical limitations. I live in a very rural setting with no neighbors near by and just my wife and I. I have my 1911 next to the bed, a 12 Ga. & AR in the closet. If the threat is imminent I use the 45, if it is some where in the house I tuck the 45 and grab the shotgun, if outside I trade for the AR with a mounted light. I practice with all three and feel confident with them.
I also live in a state that has a very liberal (in a good way) self defense laws. Only shoot if there is truly a threat(weapon displayed, running toward you, imminent threatening `action'). Shoot to `neutralize' don't make any statements to the police (other than "I was in fear of my life") without an attorney present. If that doesn't cut it where you live I'd consider moving to a `free' state.
That is my two cents for what it is worth
Armed you are a citizen, unarmed a subject.
An armed society is a polite society.
Fear the government who fears you guns.