My primary go-to gun in self defense is a 5.56 carbine with ammo that will basically explode in tissue. In my case, M193. It has a very thin jacket, and does nasty things to people when it hits them at over 2600fps. In my case, it will hit at over 3000fps, so I'm not really worried, but the bullets will not hold together when forced into tissue at that speed.
I used to be an advocate of shotguns because.............
Every helpful gun store clerk said that's the best thing for home defense, and they must know what they're talking about....right? Usually not in my experience.
You do have to make your hits with whatever you choose to shoot, and train often with it in stressful conditions, from unusual shooting positions, with intense demand for performance of multiple tasks within short periods of time. The shotgun's benefits along with hits are its psychological effect, but must be weighed with its potential for strays and over-penetration as well.
Pistols are the weakest form of firearm to fight with, in their usual chamberings.
http://www.wlwt.com/news/30470177/detail.html
Check this out. For the Grendel in home defense, I would personally lean to the lightest bullet possible going the fastest, with the best expansion characteristics, or thinnest jacket. The 100gr NBT is what I think of right now, which will go 2700fps out of a 16", and recoils fairly lightly.
A firearm and training with it is only one part of a home protection plan. There are a lot of other elements to consider, like EW systems, PACE commo plan, PACE hold-up points, vantage points, possibility for panic room, etc. etc.
For whatever blasters you choose to stage, carry, etc. for your home protection plan, shoot them enough to know that they are reliable with the mags and ammo you have, and practice clearing the different types of malf's with them. FTF, FTE, Stove, Double, Bolt-override (AR)