I wouldn't know if this specific scenario that I thought of in my head would collapse the Hellenistic era but it might drastically shorten it. Have Ptolemy Keraunos' assassination plot against Seleucus end up in complete failure. He is caught and executed. Seleucus annexes Thrace and Macedonia, adding it to his empire. Pyrrhus of Epirus, the co-ruler of Macedon with the late Lysimachus, is pressured to give up his claims in exchange for military assistance in his upcoming war in the Italian peninsula. Seleucus' intentions are to hand over his Asian possessions to his eldest son and successor Antiochus while ruling Macedonia, Thrace and Greece proper. The crown prince and soon-to-be Lord of Asia, Antiochus decides to celebrate his coronation by rebuilding the Babylonian temple Esagila.
While making a sacrifice in dedication to Marduk, the crown prince stumbles on the rubble and falls, hitting his head and dying. With Antiochus dead, Seleucus' plans on a peaceful retirement in the west are completely dashed. Seleucus appoints Pyrrhus as his viceroy in the west, marrying his daughter Phila. Having submitted the Greek cities into accepting Seleucid hegemony, Seleucus leaves a token military presence in Europe and departs to the east to train his other son Achaeus to become a proper successor to inherit his Asian and European possessions. Mid-way to his journey towards Seleucia, Seleucus passes away from old age. The news of the Seleucid king's departure soon reaches every corner of the world. The Ptolemies, long-time rivals of the Seleucids, instigate rebellions in Syria, Anatolia, Greece and Persia that Antiochus, had he lived, could have dealt with some difficulty. Ill-prepared, Achaeus demanded reinforcements from Europe to help crush the Anatolian uprisings but Pyrrhus uses the remaining Seleucid forces in Europe, including Seleucus' Indian war elephants to help subjugate much of southern Italy. He crushes multiple Roman armies and comes close to besieging the city of Rome itself but he is soon distracted by pleas to help liberate the Sicilian Greeks from Carthage and abandons Italy.
Crossing the Straits of Messina, a storm hits and Pyrrhus' ship sinks, drowning the Epirote ruler. The Kingdom of Macedon and Epirus descends into chaos and is unable to withstand the deadly combination of in-fighting and invasion by the combined Gaulish invasion led by Cerethrius, Brennus and Acichorius. Only a united coalition of Greek cities led by Athens, Corinth and Sparta prevented the Gauls from doing the same to free Greece. The Olympus Massif, marking the boundary between Thessaly and Macedonia, would forever mark the boundary between the Greeks proper and the Balkan Gauls. The Textosages would form their kingdom in Macedon. The Tolistobogii would content itself ruling over their Epirote subjects. The Trocmi received possession of Thrace and a small foothold in Asia Minor. Minor tribes would be forced to accept a more tributary status from the major three tribes turned kingdoms.
For the Seleucid Empire, the situation was bad. While Achaeus was nowhere near as adept in military affairs as his older brother or his father, he had succeeded in defeating the rebellion in Syria and had taken southern Syria from the Ptolemies, he had lost complete control of Asia Minor. Tributaries such as the Attalids of Pergamum, Pontus and Cappadocia had declared independence and conquered the territories still loyal to the Seleucids. The Fratarakas of Persia, once loyal administrators of Persia, had declared their independence and seized control of all Seleucid territories east of the Zagros. Making peace with Egypt and his former vassals in Asia Minor, he attempts a reconquest of Persia that ends disastrously. Achaeus is captured and forced to swallow gold. The Fratarakas capture Seleucia and execute the rest of the Seleucids.
The Persian Empire is once again re-born. The Gauls rule the homeland of Alexander the Great. While Greek culture continues to flourish in most of the known world for centuries to come, the time of the Greeks as a militarily ascendant culture is at an end.