Okay this is what I am thinking.
A 22 year old King looks at the opposite side of the River Granicus, and decides not to listen to his senior lieutenants who warned of the steep banks of the river. Alexander III of Macedon would mount his great charger, Bucephalus, and led his shock calvary in an audacious charge across the river and up the opposite bank. The Persian led forces fell back, and Alexander penetrated deep into their ranks. This was exactly what the Persians wanted. Alexander accompanied with few men, was not detached from the main body of the Macedonian Army and surrounded by Persians. Spithidates, an ax-weiding Persian manages to deal Alexander a mighty blow to the head, damaging his helmet and leaving the King disorientated and unable to defend himself. Just before Spithidates is speared dead by Alexander's "personal bodyguard," Cletius, he manages to make another blow on Alexander. A deadly blow.
The remainder of the battle is characterized by back and forth fighting, with eventual Macedonian loss, but recovery of Alexander's body. They head back to Macedonia.
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From here, Macedonia falls into civil war as the next ruler is debated, and the Persian's come to attack. They make ground at first, but eventually the Macedonians and Greeks find someone to rally around and throw out the Persians.
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A good 19 years later, Hamilcar of Carthage kills Agathocles of Syracuse, and sieges the city. Sicily is firmly under his control.