I just went down the same route as evorgevol while attempting to migrate one of our plug-ins to .NET 4.0, with exactly the same results.
I've now tried Andy's suggestion above, and the DLL can at least now be found. Unfortunately, Media Center reports:
InnerException System.BadImageFormatException: Could not load file or assembly 'Amulet.EPG, Version=126.96.36.199, Culture=neutral, PublicKeyToken=c364ab31ccee11cf' or one of its dependencies. This assembly is built by a runtime newer than the currently loaded runtime and cannot be loaded.
So essentially, unless there is some trick that can be played with ehExtHost.exe.config to get it to run inside the .NET 4.0 runtime (while still compiled for 3.5), it looks like this just won't work.
And even if there is a way to persuade it to work, there may be negative implications for older 3.5 apps, given that the same ehExtHost.exe is used for them all.
Anyone else experimented with this and found a way through?