I think every single person on the planet should read Yotsuba&! It's a world treasure.
It's not my personal favorite though - that would be The Voynich Hotel. I just love everything about it - great characters, funny as hell, great stories and even a great ending.
Some honorable mentions:
Since Makeine ended and nothing caught my attention this season, I'm back to browsing and binging the past, and just finished up one of the best series I've watched in a long time - Heike Monogatari.
I just happened to come across it on a stack and thought it looked interesting, so I watched the first episode and was immediately hooked. It wasn't until I saw the Science SARU logo in the closing credits that I realized it was Yuasa (though in retrospect, I probably should have from Biwa's character design).
The art design is astonishing - a perfect fit for a Japanese historical epic - with backgrounds that look like tapestries and foreground details that look like woodblock prints. It's easily one of the most visually satisfying anime I've ever seen.
The story and characters are sort of underdeveloped, as should be expected from trying to condense a sprawling historical epic into 11 anime episodes, but it doesn't feel incomplete. It's as if all of the missing content from the much larger and more detailed original epic are spread so evenly throughout the adaptation that everything that's there fits neatly together and manages to tell the story anyway.
And the way it's framed - having the narrator of an epic story of a clan brought down by their own arrogance and cruelty that was popularized by biwa singers be a biwa singer who started off with every reason to hate the Heike but who slowly came to love them in spite of their significant flaws - is brilliant. Biwa is perfectly placed to witness the story as it unfolds, and perfectly suited to recognize both their flaws and their virtues, and the inevitability of their fall.
I don't know how popular it was with westerners when it was released, so I don't know if I'm just stating the obvious, but my impression is that it's one of those that's not so much underrated as underappreciated - that it's well regarded by those who have watched it, but that that's fewer people than it deserves. Thus this post.