I'd say it's the pretext (uniting the Greeks to go after the eternal menace of the Greek world seems plausible enough, no?) the substance (the Persian wealth was unmatched anywhere in the "known world" at that point) and pure geostrategical reasons (Italy was nothing, Carthage didn't mess with the Greeks outside of Sicily... Persia was the one and only target and a little drang nach osten was the sound and productive way to go).

Had Alex lived long enough, he would go West, of course. He was too ambitious not too. But, frankly, the way he was conducting (in battle or in "civilian" life) how long could he live anyway?

Dang, the only successor (the only one that had the cojones) that could eventually unite the beast of an empire Alexander put together, was Antigonos... and he was defeated by the "coalition of the willing" (actually, of those who had more humble ambitions - ie. satisfied with a slice of the pie, instead of the full monty).