This is pretty funny CA, I've been lurking these boards for some time and signed up just to post that very idea. Beaten to the punch. =P
I would love to see what Manny did to end up in debt to "the powers that be". Preferably something like him pursuing his love or trying to clear someone's name, and in his search forsaking his friends, family and self. (I'm not trying to stake out the plot, merely visualizing the general feeling of loss and tragedy).
Sadly, the main plot of a prequel would have to take place in the land of the living, wether or not the story is told by Manny's first hand experiences or through flash-backs (perhaps he'll be able to see his own story in it's entirety in a flash of clarity as the train passes to the next world.). As frightening a place the LotL seems through the eyes of the dead as beautiful and film-noiresque it could seem through Manny's eyes the first time around, before he forgets and is reaped (if that's whats happened).
Another way of realizing a prequel could be through Manny's adventures before he began at the DoD (assuming, of course that he didn't begin there straight from death). There are many possible stories here to tell, which would help flesh out Manny's character. Perhaps through trying to rectify some crimes of his life he sacrifices even more (what if it was after his death he in-debted himself and is forced to start over his four year journey as an amnesiac working at the DoD?).
As you all can see my ideas are still pretty rough, while somewhat dear to me, I hope you won't shoot it down without atleast some discussion. =P
And last but not least, I think that whatever obstacles the plot puts in our path, the greatest obstacle is to get Double Fine to start working on this. =P