What type of Mass Effect Game do you have?
Retail Disc, Steam, EA Digital?
I think I have been one of the lucky ones. I have it both as a Retail and STEAM edition and haven't had any issues yet.
What I would suggest however is this:
Install all games to a location other than Program Files or Program Files (x86).
Either on a seperate HD or make a folder for games on C, and do Custom installations. (I make this a habit for all games)
For Example: C:/Games/Mass Effect
After installing Mass Effect, do NOT start the game.
Go ahead and download and install the latest patch, 1.02 first.
Also, while you are there, you may want to make a Bioware account and register your game.
You get free DLC, "Bringing Down The Sky" You can install this afrter the patch before 1st launch as well.
-->>If you have the original version of the game, there are know Configuaration Tool crashes in Vista and Win7 unless its patched.
Personally, I have never had to run the game in any compatability.
However, each system is slightly different so this may be a good idea. Just to be safe. It certainly will not hurt anything.