Getting Grim Fandango to work as a movie would be a difficult task, but if done well the result might be magnificent.
I think length is one of the biggest obstacles. The game has lots of dialogue that develops the characters and makes them all stand out. In a movie there would be no chance to give that much attention to minor characters, unless it became really long or had several parts. Perhaps one movie for each year.
As a result the only characters to keep their developed game selves would most likely be Manny, Glottis, Meche, Domino and perhaps Salvador, Eva and Hector. Characters like Membrillo, Toto and Chepito would either appear only briefly or be cut out entirely. And that, in my opinion, would take a lot from the experience. Especially from those who haven't played the game.
I think that any GF movie should definitely be animated. I'm thinking something along the lines of Pixar. It would have to look like the cut scenes, only even better and smoother. Most, if not all, of the music would have to be from the game and the same voice actors (at least for the main characters) would be needed. However, since at least one of the voice actors is already dead, that would be impossible unless his lines were taken straight from the game.
But now that I think of it, I think we'd get pretty much the same result if someone made a fan movie. You know, someone recorded their Full Throttle experience, got rid of the cursor and released it online. If someone could do the same with GF, only go through the best/necessary dialogue and edit out some of the walking around, we'd have a decent GF movie in our hands.