Deliberate mistake: During the flight Hughes takes with Katherine Hepburn, they talk to each other in normal, conversational voices. A twin-piston-engined aircraft of that vintage (or any vintage for that matter) is LOUD. We should be able to hear roaring engines, and the two should have to shout at each other to be heard.

The Aviator (2004)
1 deliberate mistake - chronological order
Directed by: Martin Scorsese
Starring: Alec Baldwin, Cate Blanchett, John C. Reilly, Leonardo DiCaprio, Kate Beckinsale, Ian Holm
Continuity mistake: In the dining scene where Howard Hughes' girlfriend has a sundae sitting in front of her, the cherry which is on top of the sundae changes positions in several different shots. First, the stem is turned towards the left, a few shots later, it is turned towards the right, then left again. It also shows up in the bottom of the dish, then in the next shot, it is back on top of the sundae.
Ava Gardner: You don't own me, Howard. I'm not one of your teenage whores and I'm not some damn airplane.
Trivia: At the Academy Awards, Cate Blanchett became the first Oscar winner to win her award for playing another Oscar winner.
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Chosen answer: Hughes has obsessive compulsive disorder. He washes his hands so often, and so intensely, that he's literally worn away his skin. This is common with OCD sufferers.