I work on a VB solution with three projects in Visual Studio 2010. We decided to change the target framework of the solution from 3.5 to 4.0. While doing this R# throws (feeled) several hundrets "Object reference not set to an instance of an object" exceptions. Although after changing the first project R# did not recognize references from the 4.0er project to the 3.5er projects. After changing the target framework in all projects everything worked as expected again.
[Edit] I just noticed that the exceptions are also thrown when i change the project configuration from "Any CPU" to "X86" or from "Debug" to "Release".
All exceptions where reported via the exception browser (RSRP-318xxx).