Seriesly, if I had to choose only one weapon for defense, it would be a AR15-type, or one of the fancier foreign 5.56mm weapons. It's the cartridge that's critical, and not the platform.
The 5.56mm cartridge is accurate and easy to shoot, making it easy to master. The quality weapons range from accurate to phenomenally accurate. Be sure to get some good combat optics, which double the weapon's effectiveness. Be prepared to spend almost as much as you did for the rifle.
The idea is to dominate the conflict over the broadest likely range. If you're not doing counter-sniper work, or shooting it out in the living room, the M16-type can be fast, accurate, and lethal out to 300m, if you've learned to master it.
The US military has historically engaged in firefights that average 176 yards. Police and civilian shootouts are at much smaller range. Your goal is to dominate the orc armed with an AK47 before he even realizes that he's within your range.
Again, this assumes one person, and one and only one weapon that handles the broadest range of situations. With a bit more leeway, I'd add a major-caliber handgun to my gear. Beyond that, I'd scrounge up enough buddies that the real experts with their "exotic" weapons can use their skills while the rest of us take care of "everyday" business with the 5.56mm weapons.
The El Diablo muzzle break?