You Shouldn't store games on your desktop and try to avoid storing them in C:/
Your OS is 90% of the time going to either be on C:/, or using it for main functions - and when C is bogged down, Your computer will run slower, and slower, and slower
The effects of bogged down C:/ (or OS) can be any sort've alternate issues as well, Like inability to....."house" a game as it starts running. - especially when those games are in the C:/ drive.
I would first suggest (if Possible) moving (several gigs) of the data that's on your desktop/C:/ to an alternate drive/Partition - Change download locations and etc so they don't crap all over the C:/ drive, etc.
Ensure having the system requirements necessary for running the game - if you have 4 gigs or less, It's probably be easier/better to use 32bit version, but I can't swear there'd actually be a difference on that part.
Ensure the game is properly Extracted (again, recommended NOT on the Desktop, the desktop isn't going to have problems running everything, but it also isn't designed for you to store and run games directly from it, It's designed for Shortcuts to those directories, where it "Run in/Start in" at
Ensure supporting utilities are installed or up to date, as well as drivers (Primarily for GFX)
And if nothing else seems to alleviate the issue - Try the Itch.io App - But again, I do not recommend storing/running these things from your Desktop, Store it somewhere else,
If, you only have C:/ drive, and no other drive or partition, Then make a downloads folder on C:/, and store and install games to Program Files. (and also consider getting another drive, or thinking about Partitioning your one Drive (C:/) so that it acts like two drives (or more) - again, while Desktop may work for some, things, running some games etc - it isn't exactly designed to, so some things just won't.