I've played over 80 different adventure games that I can remember, Grim Fandango is the best. The story is truly original and tons of fun to play through. Great humor, artwork, characters, dialogue, voice work, cut scenes, music, puzzles and overall atmosphere. The only thing not on par with the rest is controlling the main character Mani Calavera. He controls like a slow moving Lara from the original Tombraider. It doesn't matter much though for an adventure game, you'll get the hang of it. I love that he looks at points of interest while you walk around, instead of the careful screen scanning you are usually required to do in point and click adventures. Grim Fandango is an awesome adventure which takes you to all kinds of great places, even to the edge of the earth. Everyone should play this.
I really wish I could play this. It's often cited as a classic yet I only knew one person who owned the game and it's pretty difficult to get hands on it now.