-Drugs drugs drugs. So, the psychics need to take extremely powerful Schedule One drugs to keep the power from consuming their personalities entirely. These pills also unlock psychic abilities in people... assuming it doesn't kill them, of course. What triggered Tetsuo's transformation is his love of recreational drugs and he spends a great deal of time consuming drugs to keep himself stabilized until Lady Miyako dares him to go cold turkey, which is how the power consumes him, or to be more accurate, forces him to undergo rebirth. Tetsuo doesn't just see flashbacks of his past with Kaneda, but also his own birth and in the manga, turns into a giant fetus before exploding.
-The crazy old lady praying for Akira's return was a significant character acting the exact opposite of her manga version. So, this old lady is Lady Miyako, who was working with Nezu to get Akira under their custody. After Akira blows up Tokyo Bay, she leads the other competing faction to Tetsuo and Akira's kingdom and trains her own psychic monks because she is also one of the numbered children. I understand why she gets sidelined so hard, as she functioned mostly as the wise elder exposition character who also possesses Kei to fight her battles. Kiyoko serves that role better and technically speaking, first.
-Akira is alive. His general function is to be a silent macguffin and hair trigger bomb that turns Tokyo Bay into a crater. The movie made a much better decision to have him be dead considering the Great Tokyo Empire is really Tetsuo and Pompadour Vizier's project and Akira is a silent King reacting to stimuli for most of the plot until the very end.
-Kaori is vastly better in the movie. In the manga, she shows up as a beggar in Tetsuo's Great Tokyo Empire and survives because she was smart enough to not take drugs. Her tasks is mostly to serve as a nursemaid to Akira and Tetsuo until she gets shot in the back by Pompadour Vizier. Not as iconic as getting crushed to death.
-More psychics. Tetsuo drugs his followers so he can have his own army of psychics, so we get a lot more weirdos like Birdman and Eggman and Oversized glasses guy. As anyone who isn't Tetsuo, Akira, Miyako, and Takashi et al are jobbers, they all die.
-Ryu gets to live this time, mostly so he gets to meet the Americans Navy SEALs that show up to take Akira and kill Tetsuo and the rest of the psychics with biological weapons. Which works on the jobbers, but not Tetsuo. Since the Americans are cut out of the movie, there isn't much for his character to go.
-The Americans and I guess the Russians too. Because of Akira's appearance, the Russians take Northern Japan and the Americans deploy a carrier group for their own ends. The big climatic battle between Kei and Tetsuo takes place on the carrier instead of the ruins. Understandable why these guys were cut out because they show up to get the reader up to speed by tank 5 and thus, negatively affects the pacing in movie format. We do lose out on Tetsuo acting like Nappa and fucking over fighter pilots and him sending a satellite at the carrier group.
-The Colonol uses SOL multiple times and staged a Coup d'état. So you thought the movie Colonel was dumb to confront mutating Tetsuo with a sidearm, right? In the Manga, he uses a laser pointer thing like the Hammer of Dawn. The Coup worked until he failed to prevent Akira cratering the city, which led to the Great Tokyo Empire.
-The ending. The manga does have a more definitive ending. Kaneda inherits the Great Tokyo Empire and uses Akira (who is dead at this point) as deterrence. They do not follow the provisional government. I'm divided as to whether the movie ending is better or not. Movie ending is definitely more artsy-fartsy, but it can be unsatisfying.