I have both Xamarin Studio and the Visual Studio (beta) which are roughly the same.
So, you'll want to set it on the Project Options/Compiler page under "Platform Target". No other setting appears to matter.
Yes, the whole configuration manager thing in Xamarin Studio doesn't seem to work like I'd expect it. I struggled mightily with it. I think it may even be buggy as some settings don't seem to save.
I also discovered that if you're using the old Xamarin.Mac.Classic project to build a package it will no longer work. You'll need the newer one now to get the 64-bit packaging.