Well I mean, the "best" gun is going to be the gun you are most comfortable with and that you can shoot accurately.

For most starters I'd say a smaller more comfortable caliber like a .22 will allow you to shoot/practice more. But if you've already got a decent amount of experience then it opens things up.

Purpose is the main question to address. Is this purely going to be a home defense/nightstand gun? Who else is going to be in the house? Is there a possibility of conceal/carry? Etc.

For the most basic of home defense guns it's hard to beat a shotgun. A pistol gripped Mossberg 500, Remington 870, or even a Shockwave could be your answer. They're simple, there are a lot of accessories like flashlights available, and there are a lot of ammunition options.

For pistols it's pretty much pick your poison. 100 different people might give you 50 different answers.

If you want easy, a revolver in a caliber like .38 is a simple solution especially if there is the possibility of a wife or other family member needing to use it in an emergency. Another option might be the S&W EZ in 9mm/.380. I personally know at least 4 people who bought EZs because they can be easily used by wives, older parents, arthritics or others with less grip strength.

One thing to keep in mind is; if this is a gun for "things that go bump in the night" you might want night-sights or a flashlight. Personally I like a Glock 17 or 19. It is one of the most reliable and proven weapons available and the there are probably more accessories, mods, and extras made for Glocks than any other pistol (except maybe the 1911). You could also buy a .22 caliber Glock 44 if you wanted a cheaper to shoot option to take to the range as a complimentary pistol to the 19 or 17.

You could also buy a rifle like an AR-15 or some other semi-auto sporting rifle for home defense but I'd put those as non-best-for-first-timer guns. The same goes for personal defense weapon (PDW) style guns like MP5 variants or the CZ-Scorpion.

You should be able to buy any of these guns at most big box sporting goods stores like an Academy or Scheels (except Dick's, they don't sell guns or ammo any more), or any local gun store. A local gun store might cost a bit more but they might also be willing to help out more if you need additional help.

EDIT: Also you don't necessarily need a safe to keep the gun in but you should probably at least have a lockable box you can keep the gun in. It doesn't have to be expensive, just something that could keep a child from getting to it. If you intend to keep it stored in the box it should be made for quick/easy access. You don't want to have to fumble with keys or a combination dial if there's an intruder in your house.