There is no benefit to using My.Settings in VB.NET development.
Firstly My.Settings is only available in the VB.NET environment so it’s confusing for anyone else not familiar with the environment and a bad habit to get into.
Secondly the XML to support it in the app.config file is verbose, unwieldy, and typo prone making it difficult to cut and paste to another app.config file.
Thirdly, if you are creating a class library the settings are compiled into the DLL meaning that they cannot be altered and may be used unexpectedly.
Using ConfigurationManager.AppSettings is much easier and the XML to support it is much smaller, simpler and easier to transfer between app.config files without error.