I recently did some research on making a cocos2d app for iPhone/iPad AND Mac. I have done the iPhone/iPad route but have never done it with a Mac target. It appears that some people have added it as a target but mentioned that it is finicky and others have suggested making a separate Cocos2d Mac project that uses the same files. Any wisdom to impart here?
I believe it is absolutely crucial to have both iOS and Mac targets in the same project. Otherwise you'll spend too much time keeping one platform in synch with the other, until eventually you either manage to create a good (but still time-consuming) workflow - or end up neglecting one of the two platforms.
Ideally the code base should make as little use as possible of compiler macros. You'll want to compile both iOS and Mac code even if it's not being used for one platform. So having some classes or methods that are #ifdef'ed to Mac, others to iOS, will more often than not lead to compile errors when you switch targets. That means wrapper classes, so that you can write the same code regardless of the platform, are essential.
Right now, Cocos2D doesn't offer you to create iOS & Mac targets in the same Xcode project. The way to get there isn't immediately obvious either, because each target requires its own build settings for: Base SDK, SDK Root, Deployment Target, Architectures and possibly Compiler version. It gets worse if you also want to use 3rd party libraries (Box2D, Chipmunk, etc) because in some cases you'll be forced to create iOS and Mac specific targets for those libraries as well - if only to ensure that the library is built with the same compiler as the project's target, otherwise you can run into the strangest build or runtime issues.
I've had issues getting these platform specific targets to work within a single Xcode project without Xcode complaining or otherwise misbehaving. I haven't tried it with Xcode 4.1 and 4.2. By that time I had created .xcconfig files to host the build settings. The .xcconfig files may or may not be necessary with the more recent Xcode versions but they definitely make managing multiple platform-specific targets easier.
Long story short, the best and easiest way to do cross-platform development with cocos2d-iphone is by using Kobold2D.
Most of the 15 template projects have an iOS and Mac target in each project, you just need to select the corresponding scheme, then hit build & run. The most commonly needed platform-specific code (processing user input) is wrapped in a platform-agnostic, simple to use wrapper class KKInput.
Disclaimer: I'm the developer of Kobold2D. There's a slim chance that I may be biased. You should try Kobold2D anyway. :)