The Lost Souls Alliance!

Surely, despite the tragic sprouting of Salvador Limones and not so tragic sprouting of Hector Lemanz, the work of the Lost Souls Alliance in the Land of the Dead is not finished. The sequel could follow a new soul (perhaps initially reaped by Manny), who has to work off his time in El Morrow and is eventually recruited into the alliance by Eva... it could work.

Anything is possible, I suppose

OK, but who would be the enemy then?

Well you know how enemies function. There's always a brother\cousin\friend\etc. just waiting in the wings to jump up and declare a desire for revenge against the hero\s for the death of their brother\cousin\friend\etc. Don't you watch movies?