Unfortunately, game development is still very much a black art as a result of a lack of quality documentation in terms of the various game engines available.
However, with MonoGame, like libGDX, there is a preliminary structure for the methods in the main module, which defines a standard game loop for the processing.
I would suggest that you put as little into this primary module as possible since it is only there to handle the master game loop process. The rest of your functionality should be broken down into sub-sections of the master project or libraries that support specific functionality. This way, you can design a game in similar style to building a business application.
Structuring your game in this fashion will have little affect on overall performance since everything is processed through the .NET CLR and the MonoGame libraries.
If you would like, I could send a you an image of my own game project solution to give you an idea as to how I have set up my own work...