Calvin and Hobbs in my opinion stood out because it's targeted audience was grown up people though the protagonist of the cartoon was a kid. As adult we try to see and perceive the world through the kid's eyes.

Whether it is pointless education, our cruelty for animals and nature, hypocrisy in art, falseness of popularity surveys or just plain simple living in imagination sort of stuff , C&H not only brings a smile but it silently pays a tribute to our lost innocence of childhood.