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- And your sound card? - What kind of sample rate and bit depth do you use? - You did tried a game repair? (I know, you installed fresh, but try it anyway if you didn't yet.) 
- The sound card's on-board, device manager just says "NVIDIA High Definition Audio". My headset uses 192000 Hz and DFX uses 48000 Hz @ 24 bit (with DFX probably overriding the headset since it's set as Default Device). - When I do a repair it says "DirectX Setup Error: An internal error occurred.". It also doesn't start the game anymore, even after applying ME2IniFixer. 
- Thanks for the edit, I assumed that the game would not longer run after that error. - Go to your ">drive<:\Program Files (x86)\Origin Games\Mass Effect 2\__Installer\directx\redist" folder.
- Delete all files with the ".cab" file extension. (Only this files, the "DXSETUP.exe", dsetup32.dll and "DSETUP.dll must remain)
- Run the "DXSETUP.exe" as Administrator (right click the DXSETUP.exe > run as Administrator) > reboot.
- Test the game.
 - If you use the "ME2IniFixer" you might run some mods, if so which one? - What did you edited inside the Ini files if you don't use mods? 
- https://www.nexusmods.com/masseffect2/mods/68/ 
 https://www.nexusmods.com/masseffect2/mods/156/
 https://www.nexusmods.com/masseffect2/mods/157/
 And also ReShade.
 Now the game boots over ME2Game.exe, but not over Origin. Also, no change to the sound issue.
- Rename the "MassEffect2.exe" to "MassEffect2Launcher.exe" - Rename the "ME2Game.exe" to "MassEffect2.exe" - Now the game should start over Origin again. - As for the sound issue, try to set the sample rate to 48000 on the headset and both devices to 16 bit depth. (DVD quality) > test. 
- Alright, the renaming thing seems to have worked. - FXSE doesn't have 16 bit, only 24. I set the headset on 48000 16 bit, which resulted in a constant pervasive static, all sounds becoming extremely distorted and all voices turning into the deep voice of some demonic overlord. Alright, thanks for the nightmare fuel. ;D - Setting both to 48000 24 bit produces normal sound, although still with the tin can voices. 
 @Mettsoldat wrote:
 - FXSE doesn't have 16 bit, only 24. I set the headset on 48000 16 bit, which resulted in a constant pervasive static, all sounds becoming extremely distorted and all voices turning into the deep voice of some demonic overlord. Alright, thanks for the nightmare fuel. ;D - Well, here you get sound FX without any mods or applications. 😉 - But seriously, that your sound system is producing such distortions at completely standardised settings is odd. - I am not a big fan of software like the "FxSound Enhancer" simply because it is very complicated to say what they change inside the system and if this changes interfere even if the application is not active. - Please preform a clean boot and test the Game afterwards. - I assume you tester the sound on a ME2 vanilla Installation before you installed any mods or changed any ini settings? - Your headset is plugged to the computer via audio jack? (What I saw about that headset it should be that way.) - Please create a DxDiag in text file format and post it with your next reply. You can do that with the "choose file" button at the bottom right corner of the reply window. 
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