Ok I understand we're brainstorming here, so: 
Settings could be:

1.)

Space-Age: A group of companions on board some sort of vehicle that can handle travel within space.  The group could travel to various planets to learn about them.  A plot for this space setting could be that there is an incoming supernova, (or star explosion), that has the potential to wipe out the entire universe, leaving nothing behind. Our characters need to find a way to save the universe.  

So: Group vs. Supernova

2.)

Medieval Times with Magic

Our characters are living in a time of kingdoms, where there are wielders of magic, rebellions to overthrow rulers, spies or 'insiders' to complete 'tasks' in secret, performers that entertain and more.  A plot for this setting could be that one individual has taken control of an artifact that has enhanced their magical powers well beyond that of an average mage.  This artifact has also corrupted them, making their desires for power and violence overule everything else.  They shortly thereafter decide that the world will be theirs.  

We do not want to be under their rule, and so we work towards stopping 'the dark one.'

So: Good vs. Evil.