Have you ever seen Daria? Same idea, implemented in a very, very different way.
At heart, both are stories of alienation; both Hank and Daria are massively detached from the people around them. A large focus of both stories is how this detachment stems less from the people around them being strange, and more from the perception of both characters of those people.
Where both go above and beyond, however, is those eccentric, oddball characters. Instead of just having someone weird and letting them just be weird, they go out of their way to justify why they would be like that, and make them both believable and consistent. Well, mostly, anyway.
What's most interesting about this is a third focus, one that's a more minor point in Daria, but may well be the entire purpose of King of the Hill; the effect people have on the people around them. As I said, the main characters are both believable and consistent, but you can see clearly how they've had an effect on one another. Think about the relationship between Cotton and Hank, then Hank and Bobby[footnote]This being both the most obvious and the most prominent example[/footnote]. Both are clear results not only of their upbringing, but of their environment and even their time. Each of them are not just a part of the world around them, but are a result of the state of that world, and a reflection of it, as well, and the message that comes from that is largely positive.
Or that's what I think, at least.
