> which OS?
The one you want to run your software on.
> what GUI framework?
Assuming you aren't making a game, each OS has a different answer. Making an iPadOS or macOS app? I'd probably go with SwiftUI. Linux? I'm partial to GTK. Windows? Probably WinUI (although I also still like MFC extended with raw Win32 API calls).
There are cross platform tools, but none of them are very good. If you want to make something really great, target the most important OS and make the absolute best thing you can with the native features of that OS. Follow the conventions of the platform and you get a lot of stuff (like accessibility features) for little effort.
> The web is a single platform
I agree. The web as presented by the browser is its own distinct platform. A well written web app will almost always use more battery, memory, CPU, and network bandwidth than a similar well written native app. Sometimes, despite all the problems with web technologies, the web is where something belongs.
I'm still a big believer in the personal computer. The web takes power from individuals and is a step back to the days of dumb terminals and centralized computing.