Everyone seems to have an opinion on what would be the best home defense weapon. Get a .45, get a 9 mm, get a .38 revolver, get a rifle...it goes on and on.
First, the best weapon for the job is the one you have. Whatever you have is better then nothing at all whether it be a rifle, six shot revolver or .22.
Second, imagine the circumstances behind the defense situation. Would you be able to manuever a rifle after being awaken at 3am from something crashing through your door? Would you be able to manipulate the controls on a semi-automatic in order to get it to fire while in low light and half-asleep? Set your alarm clock for 3am and put it on a loud buzz. Then see how fast you can move around with a long gun.
Therefore, with that said, I would simply use a revolver for a good bedside weapon. This weapon is a no-brainer and is the best weapon when being awaken in the middle of the night from a deep sleep.
However, I would have other weapons around for different situations. I would have a semi-auto in .45 for when there was more time to prepare. I would have a carbine in .45 or a long rifle when there was even more time to prepare.
I like the .45 because of stopping power. I know that people are going to reply back to this thread stating that shot placement rules, however, when it comes to my life in a close quarters situation then I will gladly trust the .45 over these other calibers. Even if it gives me only a slight advantage, then I'll gladly take that advantage.