I keep a handgun next to my bed for the instant when "I hear the glass break", and a shotgun in the corner, loaded with Federal Premium OO.
Yeah, it will penetrate walls, but I use it for a couple of reasons.
I have a Vang-Comp barrel, so it patterns very cleanly, not to mention an optical sight to keep my entire pattern on target, as opposed to a bead, where you are effectivley "throwing" your pattern. I don't really have to worry about strays. If I miss with the entire load, well, it will penetrate the walls , but so will a handgun, so that argument dosn't work.
Also, I can run through my house at a full sprint with my shotgun, and havn't had a problem "handling" it, so if you aren't very coordinated, it probably isn't for you.
12ga is the best for home defense IMO, so far ahead of it's competitors, there really isn't a debate.