Getting them to make a completely unique story within the ME universe is asking for too much, imo. I'd prefer it but the likely hood of it happening is practically non-existent. It would follow the general story of the first game and be mostly romance, drama and action. Liara and Ashley might have a fight over who gets to be with Shepard. Most of the alien squad will get very small roles and those who aren't fans of the series already likely won't learn much about them as they'll be glossed over. They'll get a lot of the parts of the lore/story disgustingly wrong and fans will be foaming from the mouths. Some characters will be charged rather drastically but will get mixed results from fans because some might enjoy the changes if they didn't like the original character in the first place - it'll be a matter of debate on the forums for sometime.
In the end it will be a pretty decent movie on its own but as a Mass Effect movie specifically it will be disappointing and fans of the series will not be happy. Fortunately for Hollywood their target audience isn't really the fans but the general public and thats why it'd do okay. Will it be as bad to its subject lore as Avatar the Last Airbender? Probably not, but it'll still be bad. You'll probably question if the writer/director/actors/anyone involved in it had any knowledge of the actual game at all or even bothered to watch it on youtube. Or, at best, you'll feel that there was only one guy there that actually tried to keep things within lore but ultimately didn't get his way often enough. It'll feel like a cash-in to fans but like I said overall as a just a movie it'll be pretty good.
Personally I wish the movie would focus on the First Contact war. There's a lot more leeway there and less chance for them to mess up. Especially if the only other race humanity sees for the majority of the film is the turians. Until the end when peace comes and the story ends with us learning about the citadel and council races. That will be the cliffhanger that has people excited to see the next movie. Which will have all the problems mentioned previously. I believe that if they made one set in the time of the First Contact War then us fans could at least get one decent movie out of hollywood before they ruin it.