Fruits Basket. The creme de la creme of shojo! The artwork is flawless, the characters are endlessly endearing, and the story is more memorable and well-developed than any other I've read.
The main protagonist, Tohru Honda, takes some getting used to. She is unbelievably optimistic and almost too selfless at first, but as we grow to understand her, we love her as someone admirable and pure of heart. Not something that a lot of modern characters can lay claim to.
The main storyline seems almost sickenly cute in description: when the members of the Sohma are hugged by someone of the opposite gender, they turn into an animal (one for each member of the zodiac). It sounds like it will go nowhere from there on, but that is so wrong! Every character has its own history and subplot, and the way they intersect and flesh out is really satisfying.
I know there are a lot of great shojos out there, so I need to point out the big thing that sets this manga apart from any other for me. I cried at the end, not because of a tragic or ultra-happy ending, but because it was over. There was beautiful closure, to be sure, but I just wanted it to go on forever!
If you like shojo, this is simply a must.
P.S. I was extremely disappointed in the anime, which basically threw out a lot of the very best plot points of the manga. Turbo fail on that one.