Oh boy, that question is worthy of a thread all by itself. And there are lots of right answers. But first there are a lot more questions.
What environment do you reasonably expect to use it in? What are the most likely threats you expect to face? What is your level of proficiency with a firearm? How much time, money, and effort are you willing to put into learning to use the weapon safely and effectively?
How much money do you have to spend not only on the rifle but on range time and ammo?
In some scenarios an AR type rifle would be a solid choice. In others a lever action might be a better choice. That being said in lots of possible scenarios a bolt action center fire would be damn near ideal. In others, you can't beat a pump action 12 gauge shotgun...
If you're a relative novice, and live in a standard issue suburban area of the US, and don't want to spend a grand on a rifle, I might personally recommend a Mossberg pump action 12 gauge.
They run around $300 bucks, ammo is cheap and plentiful, and with the right load you can kill anything that walks, flys, or crawls on the North American continent.
But like I said above, there are lots and lots of questions to ask yourself before you plunk down your hard earned money on a 'long gun' for personal defense.
L
That was a rhetorical question.