I never really understood Synthesis. It sounded like the matrix of life was being changed to the extent that synthetics would forever be part organic and organics would be part synthetic but, by definition, I don't see how that could be sustainable beyond the first generation. How could babies be born with synthetic parts? Why would synthetics automatically be manufactured with organic parts unless they chose to do so? Why would they choose to do so? I just didn't get it.
Having said that, I tended to work towards specific endings by making my Shepard into the type of character who would favour that ending. As such I was happy to choose all three endings depending on the Shepard and the circumstances. For example, my destroy Shepards would be anti-Geth and would generally consider synthetics, even EDI, as just being machines that simulated life without really being any more than that. That way I had no qualms wiping them out at the end.
My Control Shepards worked to bring the Geth and Quarians together, encouraged EDI and Jeff and couldn't possibly pick an option that would wipe them out. Nor would they consider imposing a fundamental change of the physical and emotional natures of all the Galaxy's races. The Reapers are already being controlled (by the Catalyst) and replacing that control with my own has got to be better than killing them.
Synthesis actually takes the biggest stretch, for me, but those Shepards are also pro-synthetics. I just allow them to be persuaded that bringing synthetics and organics closer together so that they can choose to live in harmony without being forced to do so has got to be the best way to go.
You can roleplay it so that all the endings (even refuse) makes sense to your Shepard and thus makes the ending satisfying within the context of that runthrough.