I totally love Yotsuba&!, but it's not my absolute favorite. My favorite is kind fo a toss up. I absolutely adore ARIA and Aqua, for it's sense of wonder and pure fun, and Montster is flat out a literary masterpiece, full of excellently executed drama and intrigue, but then lastly, there's the Demon Ororon, which boast the ability to make me cry every time I read the last book D`:
With such major contenders, it's really hard to place just one. And that's already after eliminates some stong nominees (Saiyuki, trigun Maximum, Negima!, Chrono Crusade)
but thanks to this post, I remembered the one manga that trumps them all hands down. even with my attachment to ARIA and Ororon. That series is King of Bandits Jing. Take the Wonder and breathtaking artwork of Aria,with some of the sensibilities of Ororon, and even Monster, and by the Twilight tales books, you have a series of pure win.