So let's suppose the conquests of Phillip II go as OTL, then we get our PoD -- maybe his assassination is prevented, maybe Alexander is not the heir, or comes to power with a different personality. Whatever the detail, the general effect is that Macedonia and the Achaemenid Empire still go to war, and the Persians still get badly beaten -- but the Greeks decide to content themselves annexing Anatolia and the Eastern Mediterranean, while supporting an Egyptian rebellion; the army may march toward Babylon to make sure Darius is good and crushed, but the lands of Mesopotamia, nor those to the east, are not conquered.
How does this change history over the next century and beyond? How is the Mediterranean world affected without the Selucid Empire as a player? Or with a non-Hellenized Egypt for that matter? Can Rome still rise to superpower status in such a world? What is the fate of the chastened Achaemenid Empire? And does this (again, over the next century) have butterflies beyond; for example, will Chandraguta still found the Mauryan Empire in India?