I want to be able to have two instances which are completely independent in the sense that I can be working on two separate unrelated projects in different folders without any interference.
(Spyder maintainer here) This is easy. You need to go to:
Tools > Preferences > Application
in Spyder 5, or
Tools > Preferences > General
in Spyder 4, click the "Advanced Settings" tab, and deactivate the option called
[ ] Use a single instance
Then every time you start Spyder a new window will be opened. If you want the old behavior back, just activate that option again.