There's nothing wrong with the .30'06 for defensive use. With a high velocity light expanding round it's going to make quick work of anything. Overpenetration concerns are overplayed when it comes to rifles and underestimated when it comes to handguns. Slow and big handgun rounds will typically pose a far greater threat than supersonic expanding rifle rounds. And they're more likely to miss and go flying off lord knows where.
The Garand, however, has some drawbacks as a home defense firearm. The safety catch is not the best design for this purpose, and it was not really designed to be toted or stowed with one in the chamber. I could see a potential ND there with one's finger poking around the trigger area trying to engage or disengage a safety in the middle of a rather tense situation. If you do go down that path, I'd suggest using Israeli presentation methods and IGNORING the safety. Just chamber if the need arises. After the threat has resolved one way or the other, carefully eject the live rounds entirely in the accepted fashion for Garands. Never even touch anything around the trigger.
It's also heavy and bulky even in "tanker" format. There's no real place to mount lights or optics without mods. And the action is designed to work within pretty narrow confines of ball ammo without tweaking. I don't know how reliable it would be with some kind of alternative light high speed ammo or slower home defense ammo.
In short, it can be done but there are better long gun options. I'd rather have a Mauser or Mosin if it came down to using a war rifle for defense. Lighter, better places for a light with a barrel clamp, no pressure issues to worry about, reliable feeding, etc.