I would say Calvin and Hobbes for sheer brilliance in the writing, spot on commentary on human nature, great characters, and oftentimes amazing depictions of Calvin's fantasies.

Yeah, I'm a major fanboy for Calvin and Hobbes.
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Calvin & Hobbes is the best for me. Calvin & Hobbes brings together all the elements of a great comic strip. We see normal kid in normal kid situations, but his reactions are totally bizarre. Who else would make duplicates of himself just to get out of homework, and then create those duplicates using a cardboard box?
Source(s):
http://en.wikipedia.org/wiki/Calvin_and_Hobbes

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Peanuts. A true classic and so funny and smart.
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I loved Bloom County. Close second - Doonesbury. I think it must of been the ability to laugh at hypocrisy, even our own.
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Pogo. Walt Kelly was a genius,
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Hundreds of comic strips have been published in newspapers. The majority are terrible, and almost all the rest are mediocre. There have been maybe four or five good comic strips in the history of the world. So saying that Calvin and Hobbes is the best comic strip ever doesn't really hold a lot of weight.

And it's really a shame that it's so difficult to quantify this strip's greatness. I can confidently state that Calvin and Hobbes outclasses the rest of the comic strip world more than anything else has ever outclassed the rest of its medium. Sans this strip, the industry is characterized by guys sitting on rocks making stupid puns, a Family Circus kid misunderstanding the meaning of a word, or an overweight father playing golf while telling jokes such as I LIKE GOLF and GOLF IS HARD. It's a medium that doesn't really deserve something as good as Calvin and Hobbes, but it got it anyway, and the newspaper-reading world was made a better place by it.

Calvin and Hobbes ran from 1985 to 1995. Bill Watterson drew thousands of strips, and while I wish like hell that he would come back and draw more, it's probably best to reflect and be thankful for what he's done. Below we have showcased, in no particular order, some of our favorite Calvin and Hobbes strips of all time. If you love them as much as we do, let us know if you think there are any that we should have included. And if you missed out, well, hopefully we can give you some idea of why Mr. Watterson is our hero.

This is the most beautiful, honest, touching and hilarious comic strip ever made. I would not be who i am if it wasn’t for Calvin and Hobbes. Nothing will ever top it - ever

Calvin is an unbelievably intelligent six-year-old. Hobbes is his tiger friend who plays the role of Jiminy Cricket, casual observer, and savage beast. This strip introduces their dynamic rather well. Calvin's a grossly misbehaving child, and no matter how he tries, he can't betray his nature.

It's kind of refreshing to see a strip that doesn't feel the need to have an uplifting message, or feel like it needs to point out that it's mean to whack an innocent person upside the dome with a snowball.
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Sinfest.

http://www.sinfest.net/comikaze/comics/2007-03-26.gif

http://www.sinfest.net/comikaze/comics/2007-05-13.gif

http://www.sinfest.net/comikaze/comics/2007-11-29.gif

http://www.sinfest.net/comikaze/comics/2007-11-30.gif

http://www.sinfest.net/comikaze/comics/2007-12-17.gif

http://www.sinfest.net/comikaze/comics/2007-12-30.gif

http://www.sinfest.net/comikaze/comics/2008-06-29.gif

http://www.sinfest.net/comikaze/comics/2008-09-21.gif
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You'know I really want to post another Calvin and Hobbes strip, but that would be overkill. C&H is the best answer for this question but I do want to give my 2nd favourite.

Garfield... actually make that Garfield Minus Garfield

If you are not aware, check it out, it is a hilarious new take on the old Garfield comics, done by a random internetter with lots of time and good idea, so good actually Garfield creator Jim Davis applauded it and put out a book.

http://www.flickr.com/photos/33749589@N07/3312733361/

here is a small taste, but I can paruse this site for hours and never stop laughing, great stuff.

http://www.flickr.com/photos/33749589@N07/3312735043/
Source(s):
http://garfieldminusgarfield.net/
http://www.mahalo.com/Garfield_Minus_Garfield

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Lil Abner. If you only saw the last few years you may be unaware of how funny and how pointed the strip originally was.
Source(s):
http://www.lil-abner.com/

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