Just confirming that I have the same issue, so its not unique. I note that after the initial program launch when the issue occurs the game deletes gameSettings.cgs and creates a new userGameState.cgs file, which naturally means all options, settings, Paradox login, achievements etc. are also reset. Quit and relaunch and the game works fine (albeit with the aforementioned nuked settings, of course).
I work around it by keeping backups of my userGameState.cgs and gameSettings.cgs files and manually copying them back into AppData\Local\Collosal Order\Cities Skylines after quitting the game when the issue re-surfaces; when I relaunch the game everything is working fine with all my settings restored from the backup. Annoying, but workable.
I originally thought it might be a Steam connection issue (I run Skylines on a laptop which moves between several networks each day), but my testing has been unable to determine a reliable pattern. Sometimes it works fine, othertimes the issue arises.
ETA: I also run Windows 10, and running as Admin doesn't solve thje issue for me.