Shotguns are the best thing for home defense. The most popular for home defense would be the Mossberg 500 or the Remington 870. If you want a safe, it might be better to go with a pistol and store it in one of those quick code safes you keep in a drawer or under the bed. As far as caliber goes, stay away from anything under 9mm. Small rounds such as 22LR, 25 ACP, 32 ACP, and 380 ACP don't have enough penetration to really stop anyone. If you are at the point where you are shooting someone to defend yourself or you family, shoot to kill. I would suggest 9mm or 45 ACP over the 40 S&W because they are easier to control and allow for an easier follow up shot. For pistols I personally love Glocks, Sig Sauers, and 1911's. Stick to the standard makes such as S&W, Sig, Glock, H&K, Springfield, Beretta, etc. (I would suggest staying away from Taurus because they have reliability issues.). In the end, the pistol you should get is the one you will practice with often and like to shoot.
For home defense: Shotgun > semi-auto rifle such as AR15 > pistol