It’s no longer possible to write a single app that takes advantage of the full range of Mac OS X features. Some APIs only work inside the Mac App Store. Others only work outside it. Presumably, this gap will widen as more new features are App Store–exclusive, while sandboxing places greater restrictions on what App Store apps are allowed to do.
via Michael Tsai – PDFpen and iCloud. My largest long-term fear of OSX is that Apple will slowly turn off the ability for applications to be useful without using the App Store and thus some Apps may just not exist anymore (SuperDuper is the easy example).