The recommendations as you can see from these posts are very numerous. If you haven't yet taken a basic firearms class, then do so. Check with your local gun shop or this site at the NRA can help...
NRAInstructors.org - Portal for NRA certified Instructors, NRA Education and Training
Next, go to a range that rents guns and try everything you can get your hands on. It's fun and educational.
If I was looking for a single handgun for home defense, I would stick with one of four calibers: 357, 9mm, 40, 45.
357 is the revolver of that group. You can shoot everything from low power .38's up to bone shaking magnum rounds through them. They are probably the most versatile handgun chambering available.
The other calibers are all semi-auto's.
9mm is the most prevalent round out there, and because of that will be the least expensive of the four. And that means you can shoot more for your dollar and get more proficient.
40 is the in between round. That's the round I started with. It can sometimes be a little snappy depending on the pistol you have, but it is effective. I think 40 is the most common round carried by law enforcement.
45 is big and slow compared to the others (that's not a bad thing). It is one of the most effective hand gun rounds ever developed.
As for pistol makes? We could go on and on and on. Myself, I like Springfield, Ruger, and Smith & Wesson. But there are plenty of others worth considering as well.
If you plan on concealing, pay close attention to the width of the gun. Width is probably more of a factor than length in concealability.
How much do you want to spend?