You're talking about an OS that is the collaborative effort of countless people. If you run nothing but stable software you MAY be safe for a time.
As mentioned before, you would be surprised how small a thing can trash your entire HD. In my first year, I tried running in root alot because, well, back in the days of Fedora-core 3, there weren't as many fancy ways to admin your system from user.
At the time, I made a small xorg edit without backing up, because I didn't think it would hurt. Desktop gone. Then I tried to fix it manually, but couldn't figure out what I'd done, exactly. Later, I thought that maybe I could reinstall my drivers and desktop, but inadvertedly disconnected my ethernet, since it was also nvidia.
While running Arch for the first time, I ignored warnings to create a user and ran as admin for a while. I installed a package from AUR that I needed and after I rebooted, my entire install was busted.
Since I was in root, fixing these problems became a lot worse than they needed to be.
You might conclude I was just incompetent. But as others mentioned... typing "sudo" is a small price to pay for some peace of mind.
EDIT: Oh... and certain programs, like WINE, are expressly not supposed to run in a root environment. http://wiki.winehq.org/FAQ#head-96bebfa287b4288974de0df23351f278b0d41014