If you try to build a solution that has a mixture of target frameworks (3.5 and 4.5.1 in my case) there are two problems that occur.
In the settings.props you can only set one target framework. This can be worked around if you add a condition that ignore particular projects (or potentially just removed this entry in settings.props entirely)
If you're running FxCop it tries to analyse all of the resultant assemblies in one call to FxCop. FxCop errors when you try to do this as it has to resolve two different versions of the framework assemblies, which it can't.
If you try to build a solution that has a mixture of target frameworks (3.5 and 4.5.1 in my case) there are two problems that occur.