Synthesis is well suited to strongly story-driven role-playing where the main issues center on a struggle for self-definition against differing ideologies. The core of the system is rules that revolve around the Self Trait, which drive action that is character-centric.
Synthesis requires that the play group devise a Story Premise. A Story Premise is a question, which the play group addresses by actually playing the game. Synthesis supports a theoretically infinite set of these, but certain Story Premises work better than others. Namely, you will find it fairly easy to make Story Premises that somehow address something starting with "self-". Self-respect, self-destruction, self-sacrifice, self-worth, and so on can be used as "seed words" to make a fuller Premise. One can use other ways of coming up with a Premise, of course, but keep the focus of Synthesis in mind.