January 2017 - last edited January 2017
Go to your ">drive<:\Program Files (x86)\Origin Games\Mass Effect 2\Binaries" folder and make a copy if the "MassEffect2.exe".
Then rename the "ME2game.exe" to "OLD_ME2game.exe".
Now rename the "MassEffect2.exe" to "ME2game.exe" (without the quotes) and try to start the game from the new created "ME2game.exe"
If that don't works, delete the "Mass Effect 2" folder in your "Documents\BioWare" folder. (The "Mass Effect 2" folder under "Documents", not the game folder!)
Then delete the "ME2game.exe", the "OLD_ME2game.exe" and the copy of the "MassEffect2.exe" from your ">drive<:\Program Files (x86)\Origin Games\Mass Effect 2\Binaries" folder.
Now delete the "Data" folder under ">drive<:\Program Files (x86)\Origin Games\Mass Effect 2"
Start Origin, go to your Games library and start the Download of ME2 again. (Don't worry, it will download a few files only.) > test.
September - last edited September
Ok guys, I think I might've stumbled onto a solution to the not-launching problem. I don't know if this happens to you as well but you can try to replicate it. I will give you my steps I did and wish the best of luck to you that it works as well.
Main giveaway: This solution lets you start ME2 WITHOUT ORIGIN RUNNING.
Quick intro: I've tried every last tip I found online. From renaming the exe's over the "put origin offline" trick to preventing the game to sync. Nothing worked. I've also talked to the EA-Staff via chat and nothing helped. Clean Origin cache here, let me check your DXDIAG there and so on. No solution in sight. Beforehand, I reinstalled everything from scratch and it did not work. My Windows 10 Home Edition is fresh (installed it clean 3 weeks ago) and all drivers are up-to-date. Hardware is Ryzen 3 3600, 16gb ram, 2070 super. Nothing out of the ordinary.
I don't know if this is a permanent solution but if you have tried out everything else and nothing worked - this could be your saving grace as well :-)
Good luck out there Commanders and I hope this could help you!
Do NOT mess around with the Coalesced.ini file!
It's your configuration file. I tried to change the mouse speed and as soon as I fiddled with it, the game would not start again. After replacing it with the saved original everything was fine again :-)