Well..historically, Alex did okay at Granicus and many of the satraps of Asia Minor either joined him or had been killed or did not resist successfully.
Memnon of Rhodes, the Greek "mercenary" (since his wife, Barsine, was the sister of a Satrap, he was more of an official Persian commander) whose "mercenary" command had supposedly been wiped out at Granicus (or was it? the sources are contradictory) was put in charge of the war against Alex. Which he did by using the Persian fleet based in Halicarnassis.
After falling in a river and getting a new mom (here is Wikipedia on this odd detour of Alex's:
Eventually, the Persian fleet sailed to Halicarnassus, in order to establish a new defense. Ada of Caria, the former queen of Halicarnassus, had been driven from her throne by her usurping brother. When he died, Darius had appointed Orontobates satrap of Caria, which included Halicarnassus in its jurisdiction. On the approach of Alexander in 334 BC, Ada, who was in possession of the fortress of Alinda, surrendered the fortress to him. Alexander and Ada appear to have formed an emotional connection. He called her "mother", finding her more amicable than his megalomaniacal snake-worshiping mother Olympias. In return for his support, Ada gave Alexander gifts, and even sent him some of the best cooks in Asia Minor, realizing that Alexander had a sweet tooth. In the past, Alexander had referred to his biological father, Philip, as his "so-called" father, and preferred to think of the deity Amon Zeus as his actual father. Thus, he had finally managed to divorce himself from both of his biological parents)
Okay so Alex headed for Halincarnassis, and was about to enter the city by treachery when Memnon opened up on Alex with catapults and unleashed the infantry that had supposedly been wiped out at Granicus. Apparently, this was one of those 10 or 15 times where only luck saved Alex from a messy death. Here's what that might have looked like in game terms (Alex is rallying his men, Memnon is attacking and the Macedonian Hypasts off-map working on getting into the city and knocking out the catapults):