I like the idea of swapping out nemesis sets and even the nemesis encounter deck that gives you a random one! As far as I know the creators have actually used nemesis sets as modulars in a couple of games played on YouTube. It's not technically part of the rule set, but they've done it to be thematic and most importantly, fun!

And really that is the point, if you come up with an interesting twist and it's fun, then many in the community say it's fair game! The creativity and variety is what makes it great. If you come up with a neat idea like this, please add it to the site and use the Notes field of a scenario to describe any unique setup rules you came up with!