The first answer here is not really one of caliber. The start for home defense should be a hardened perimeter. Good outside lighting with motion sensors, good solid doors with secure deadbolts and security film on windows will go a very long way towards keeping you from hearing something going "bump" in the night.
If you have good home security, you will have plenty of warning to get to whatever weapon you choose. Given enough time and power tools, it would be possible to break into my house. My wife and I would have plenty of time to wake up, get dressed, call the authorities, arm ourselves and get a pot of coffee going for when the police arrive.
All that being said, my immediate access weapon is a Ruger SR 1911 loaded with Speer Gold Dot 45acp 230 grain GDHP. My wife is partial to her Glock 19 with Speer 9mm 124 grain GDHP