Biggest issue with using Photoshop in your actual production pipeline: "programming in the large" - you can't do code reviews or merges on PSD files, not nearly as easily as .cpp files. So as a team gets big, it is very hard to scale up.
Often the tools (Flash [not Flex], Photoshop, etc.) you use as a small team of <10 people just do not work when you have 20-50 people working on the same project. Then again, maybe teams never should get that big!