When comparing itch.io vs Ren'Py, the Slant community recommends Ren'Py for most people. In the question“What are the best tools/sites for self-publishing books?” Ren'Py is ranked 1st while itch.io is ranked 2nd. The most important reason people chose Ren'Py is:
Available on Windows, Linux, OSX, iOS and Android.
Specs
Ranked in these QuestionsQuestion Ranking
Pros
Pro Everyone can release a game on itch.io
Everyone is free to use itch.io for the distrubution of their game, free or paid.
Pro No accounts required for buyers
It allows linking an itch.io page where the customer can just click to buy.
Pro Allows sellers to set their own revenue share
Makes it one of the best places to support your favorite creators as there is no limit as to what you want to set for the platform fee since it can be set all the way down to 0% or set as high as 100%. It is up to the developer to pick what they would like.
Pro Pay-what-you-want model with optional enforced minimums
Users can pay any amount they want to for a game, down to a minimum specified by the uploader. The minimum can be zero. A user can go back and pay more later if they want.
Pro Mostly self-service
Change prices or the design of your page at will. No need to give lead time if you want to offer a sale.
Pro Best discoverability out there
It's where unknown indies find and buy games from other unknown indies.
Pro Cross-platform desktop client
Desktop client available for downloading games and auto-updating.
Pro Offer preorders
You can start selling your game before it's finished.
Pro Cross-platform
Available on Windows, Linux, OSX, iOS and Android.
Pro Active and friendly community
Pro Reasonably good at creating puzzle and point-and-click games
Cons
Con No DRM Service and itch customers can just share your games and apps
They say they do, but you actually need a server to achieve it. They make things over complicated on purpose, because they hate DRM in nature. That's why they cannot be a popular game platform. They don't protect indie developer's game at all.
Con Very very indie
If production values and braod appeal are a thing you cherish, pass your way. Curation standards aren't mainstream at all there.
Con No quality control
You can upload and release almost anything in any state on itch.io
Con Not for every genre
While technically capable of creating 2D games in any genre, Ren'Py excels in creating visual novels and has a reasonable feature set for creating puzzle and point-and-click games. Other genres are best tackled by other engines.
Con Outdated Documentation and official built-in tutorials
Unfortunately, you will have to hunt relevant info on how Ren'py script works. The Ren'Py dev has the working tutorials on his Patreon, other than that you might as well just code in Python.