Yotsuba&! is best slice-of-life anything.
Most series in the genre focus around a group of girls as they go about life. In real life, you'd expect these girls to talk to other people, but no. All you see is a bunch of girls with a few side characters. This is completely unrealistic.
Yotsuba, on the other hand, often interacts with people that, just like in real life, she will most likely never see again. When not on vacation or adventuring about, Yotsuba is in the same setting constantly.
My point is, with other series, the 'slices' of life are often very thin, and give you little insight into how the characters' days actually went. With Yotsuba&!, you see 30-70% of her actual day.
Plus, she's our fucking mascot.