So, about profiles. You have probably seen this string default/linux/amd64/10.0/desktop before. A profile actually is something pretty simple- a set of predefined defaults for e.g. use flags, system set, package and use masks, ... The main purpose of the desktop profile, which many people use, is to provide sensible defaults for a typical desktop workstation, i.e. enabling useflags like "consolekit jpeg png". Profiles are inheritance-based, meaning this desktop profile inherits defaults from linux and from amd64. You can select your profile with eselect profile, but in the end whatever that does is only redirect the symlink /etc/make.profile to the appropriate target in /usr/portage/profile.
eselect profile also provides a list of profiles to choose from. Here on my laptop this is
huettel@porto ~ $ eselect profile list
Available profile symlink targets:
 default/linux/amd64/10.0/desktop *
The list comes from /usr/portage/profiles/profiles.desc. However, if you are brave (or insane), nothing keeps you from manually pointing your /etc/make.profile symlink to a different directory. As it turns out, there is a worthwile target hidden away, which provides a "hardened desktop" profile:
huettel@grenadine ~ $ ls -l /etc/make.profile
lrwxrwxrwx 1 root root 52 24. Jan 18:45 /etc/make.profile -> ../usr/portage/profiles/hardened/linux/amd64/desktop
So, if you want to void all your warranties, set your symlink like this and your profile will inherit from both hardened and desktop profile. Then follow the rest of the guide for switching to hardened.
What will you lose? Mainly, nvidia-drivers, ati-drivers, and skype. All three do at the moment not play nicely with hardened protection features. At least in the case of skype that is pure lazyness by the company; the programmers of skype could easily fix it if they wanted. In addition, the security benefits will lead to a performance hit; how much I cannot really judge yet.
What will you gain? For example, Stack Smashing Protector (SSP), Position Independent Executables (PIEs), Default full binding at load-time (BIND_NOW), ... There's a lot of documentation on hardened floating around, and I'm only just learning...
I'm running a full KDE desktop with radeon driver and accelerated graphics, so far I have not noticed any unpleasant side effects yet. I'll stay with it. :)