Although I haven't tried it, you should be able to run 2 Content Delivery applications on separate versions of .NET in Kentico Xperience 13.
Since all the communication in Xperience between Content Delivery and Content Management is performed through the database, you could have 3 Azure App Services with the following setup:
- Content Management (Web Forms) - .NET Framework 4.8
- Content Delivery (MVC) - .NET Framework 4.8
- Content Delivery (MVC) - .NET Core 3.1 or .NET 5.0
The two Content Delivery applications would be running different sites (domains).
These could all run together without needing the Content Management app to make changes.
Likewise, if you were to switch the Content Delivery application from .NET Framework ASP.NET MVC 5 to .NET Core 3.1 ASP.NET Core (or .NET 5 ASP.NET Core), your Content Management application should not need any configuration updates.