Last night I played with Paint.Net for a while and got it running on the native 64-bit CLR with whidbey... Pretty cool stuff!!!
Actually, a while might be overstating things... It took longer to install a copy of VS 2005 on my clean AMD64 machine than it did to get Paint.Net running natively, in fact there were no code changes needed to get it to run on .Net 2.0 (just had to change a couple project settings) and only 3 small changes to the code to get it to run on 64-bit (the biggest being removing a dependency on some assembly code used to figure out whether or not a machine has HyperThreading). All of this took < 20 minutes.
Check out a blog about Paint.Net here: http://blogs.msdn.com/rickbrew/
Here's some screen shots to whet your appitite
Paint.Net running on 64-bit CLR
Copy and Paste between 32-bit and 64-bit versions of Paint.Net
A 2GB image in Paint.Net, note the 4GB memory usage (it actually has a 6GB VM footprint at this point, yes... this machine does have a lot of RAM).
Note: this is all running on a "very close to done" internal Beta2 .Net Framework.