Hmm.... I'm split between two in particular. Steel Ball Run, and One Piece.
For one, Steel Ball Run, from Art to Story is a work of art unlike anything I've read. It's brilliant story of maturity, destiny and life. It never fails to thrill, and it's ending always leaves me with this feeling of stillness that none of the previous parts have, that nothing I've read ever has.
Meanwhile, One Piece is the manga I spent most of my Manga-Reading Journey reading. It has it flaws from time to time but it is one of the greatest fantasy stories I've ever read and has managed to maintain quality in a continuing story for DECADES. That's more than just impressive, that's rare.
YET, once more of the SBR Anime itself comes out, and ever since One Piece's Elbaph Arc which's beginning really has begun to make my love for One Piece sour just a bit, I think SBR won't just be my favorite no.1 manga, nor just my favorite no.1 anime, but my favorite story in general. or at least up there with LOTR and BCS for me.