Put quite simply, armor.

The Greeks were well-armored enough to protect from Persian arrows for the most part. Additionally, the Persian infantry were very lightly equipped. The wicker shields common in the east were fantastic against arrows, but possibly too light for combat with hoplites. There is some debate about the effectiveness and construction of wicker shields, but Persian armor on the front lines was definitely underwhelming.

When you get to the Macedonian sarissa phalanx, it becomes more lopsided. The sarissa was an enormous pike up to 18 ft long, 5 rows of spears would be in front of the first soldier. The average persian spears were around 6-7 feet. The lightly equipped Persians had very little chance of ever getting in range of a Macedonian phalangite without sustaining serious injuries in the process.

It's also important to mention the tactics used by the Persians. During their invasions of Greece, they were often over confident and hasty to end the war. This led to repeated blunders that played into the strengths of the Greeks.

Despite first appearances, the Greek hoplites were extremely vulnerable to Persian cavalry. The battle of Marathon for instance was basically just a mad charge once the Greeks saw the Persian cavalry leave the main force. The Macedonian cavalry was phenomenal though, covering the biggest weakness of the Greek way of warfare. This, along with his own tactical genius, is what allowed Alexander to basically steamroll the largest empire in their area of the world.