When comparing Microsoft XNA Game Studio vs Genome2D, the Slant community recommends Genome2D for most people. In the question“What are the best 2D game engines?” Genome2D is ranked 47th while Microsoft XNA Game Studio is ranked 80th. The most important reason people chose Genome2D is:
It's the fastest gpu-based framework out there for flash. It's beautifully optimised. It has very low rendering latency, low level OpenGL calls that other tech simply cannot do (ie Unity) due to Stage3D, and thus can render a lot more data quicker
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Pros

Pro Easy assets
it is very easy to import your own 2 dimensional assets

Pro Very easy to use
relies largely on drag and drop elements and has been used to create notable high quality 2d games such as DLC Quest

Pro Lightning fast
It's the fastest gpu-based framework out there for flash. It's beautifully optimised. It has very low rendering latency, low level OpenGL calls that other tech simply cannot do (ie Unity) due to Stage3D, and thus can render a lot more data quicker
Pro Cross-platform mobile, desktop and web
Supports Windows, Mac OS X, Linux, iOS, Android, Web and native Flash.
And with the HTML5 export, it also potentially supports development for the Wii U :)
Pro Haxe!
Haxe is a strictly typed programming language that saves development time but still compiles high performance executables, and can build for tons of different platforms (flash, c++, html5, java, c#, etc.)
Pro Access to direct draw features
Has access to direct draw features so you can make you own rendering structures (scene graphs etc).
Pro Automatic dynamic batching
Automatically batch geometries with dynamic batching techniques (by using constant buffers).
Pro Component based architecture
Cons

Con It's dead
It is not getting updated and Microsoft does not recommend using it anymore.

Con Limited platform support
Only supports Xbox 360, Windows and Windows Phone
Con Lacks documentation
The API documentation is minimal, there's not many tutorials and the ones that are there are very small and only cover the basics. If you want to learn how to properly use it, you have to ask the community or read the source code and figure it out.
Con Not too many games to showcase it
Con Slow development rate
