We are running in a SP4 / XP FR3 environment. I haven't had many issues creep up yet, but the setup is only a month old.
We did have an error with the hotfix MS0-039. Seems these fixes screwed with the printing spooler, and I had to spend some time fixing that. There is a User/SID issue I'm chasing currently that came up at the same time as the hotfix, but again this is related directly to the hotfix, and not SP4 itself.