I think I first encountered Shoulder-a-Coffin Kuro all the way back in the Borders days, when Yen Press first began publishing it, and before it went on its extended hiatus after volume 2. It was one of the first 4komas I've ever read, and completely sold me on the medium. And as also shown by Kiyuduki's GA (also excellent), Kiyuduki is a master storyteller, who not only uses the 4koma style to its full effect but also elevates it as a medium in and of itself.
Others have already delineated what makes this story so good: it's good at a whole host of things. It's clever, adorable, sweet, and extremely, extremely thoughtful. Its characters are full-fledged, and even though Kuro starts off as a bit of a cipher, she ends up having so much hidden depth, as well as growth. That's not even mentioning Nijuku and Sanju, who are adorable little beings (who actually act like children), and steadily become the heart and soul of the series along with Kuro.
I think the closest comparison with Shoulder-a-Coffin Kuro is Kino no Tabi. They actually have a lot in common -- they're a series of vignettes connected by a traveler (who's often mistaken for a boy) and their talking-whatever companion. (A bat for Kuro, a motorcycle for Kino). The difference, though, is where they end up. While Kino's backstory is just that -- a backstory -- Kuro's backstory is actually the backbone of her character, and as it slowly gets revealed, so does her inherent humanity, and the true meaning behind this entire journey. Unlike Kino, who remains untouched by everything she sees, Kuro is constantly being touched, and touching others, throughout her journey, even when she's reluctant to do so (for good reason). Even though we join Kuro late in her journey, we still see Kuro develop and grow and change as a person throughout. And all the characters she touches makes reappearances near the end, and as fun little side adventures we catch glimpses of in between Kuro's own journey.
And, ultimately, Shoulder-a-Coffin Kuro is a deeply hopeful manga. It's about believing in not only yourself but also the others who have journeyed with you. It's not about changing the world but about changing the little corner of the world that's yours, and changing yourself and others for the better through your actions. I actually almost couldn't stop the tears at the last volume because it was just so, so beautiful, and the perfect capstone on this long, long journey of Kuro's. As Kuro says, this story isn't a fairytale -- but that's what makes it so beautiful, because people can choose a different ending aside from "death" or a "happily ever after". In the end, as cheesy as it may sound, people can choose to accept the journey itself, and in doing so, accept themselves as well.