Finally got the R3 HS2 repack working on PopOS so thought I would share, I used Lutris but steps should be transferable to cli wine with winetricks.
Base game will run fine without problems (using lutris-5.7-x86_64), but there will be no translation or mods (including uncensor).
Not sure exactly which steps are absolutely necessary as I'm not a wine guru but this is what I did.
To get the mods working I had to first enable both DXVK and Esync in runner options, then add two DLL overrides 'winhttp=n,p' and 'UnityPlayer=n,p'
That will let you run HoneySelect2.exe but to run initSettings.exe you have to install a few things with winetricks.
open winetricks and install d3dcompilier_47, dotnet45, dotnetcore2
I also installed allfonts but not sure if that's necessary (and have mono installed locally).
Thats it then InitSettings.exe should run, I got a black screen but rolling over where the buttons should be makes then visible and they all work, once the actual game starts everything works flawlessly.
Happy Linux gaming