Depends what you want, you want everything GTK? then stick that in your portage config. X? then go for it. An interesting thing with gentoo is that if you don't want to set a global use flag for something, or can't forsee all the possible flags you'll need,
emerge -av some_app
will bring up the use flags and dependencies for the app you're looking for. Then manually set use flags for each one you need, if you need to. A good tool called flagedit is a clean, simple way of doing this.