Well, Commander Shepard can be an extremely different character in appearance and demeanor depending on who's playing him or her. I think anyone who's experienced the games can agree that it's just weird seeing other Shepards. It's like, the "real" Shepard is the one you've gone through two adventures as. Not your friend's, not the default one they use in marketing, and not the actor who may potentially play him. Yours is the real one.
While that's certainly no concern to the people involved in the film, it's only one of many issues that can be avoided by telling an original story. As I said on the first page, the Mass Effect universe is definitely rich enough to support a unique story that is in no way tied to the plot of the games. The best course of action is tell the story of humans discovering the Prothean ruins on Mars, the First Contact War, and humanity finding its place in galactic civilization. That way it stays true to the spirit of the games without screwing up the game's story.