First of all the term "home defense" is pretty broad. Let's say a person is qualified and wants a weapon to defend his family against the crazy who might come knocking on his door at 3 AM. A shotgun would be intimidating enough but it is unwieldy and hard to get to in an emergency. A handgun seems to be ideal for late night emergencies but I personally favor a wheel gun (revolver). You don't need to check a safety or feed a magazine or see if there is one in the chamber. The Tauris "judge" revolver is ideal. A revolver that can shoot a .45 or a 410 shotgun shell.
The best self-defense weapon for the home is whatever one is comfortable and proficient with.
For me in the home it’s a Colt 1911 – perfectly safe in condition 1 and ready to use with a quick flick of the safety. It chambers a highly effective round on a reliable and manageable platform.
For those of us in rural areas who need to defend our property outside of the home, such as during a tropical storm/hurricane, an AK or SKS is the perfect weapon; both also chamber an effective round, are utterly reliable, and as used only at short range, accuracy is not an issue.