I've been using Debian since Etch. It has been one of the EASIEST distributions out there to use. It has a low resource footprint (with GNOME & Xfce), and pretty easy to configure. I've been using Debian on a my server the last week or so (using Debian Lenny), and it has been a godsend. It's about 8x faster than using Windows Server 2k8, and supports Mono (for a game server). The package manager is just amazing. I love aptitude; it makes life so much easier. Also, the community for Debian is huge. I can get support within a matter of minutes, whether in IRC or on a forum.
As much as I love RH, I just had to put this in 2nd place. I haven't used Fedora that much, but for reason, it can be a pain in the ass to get something to work. I've used Fedora on my desktop for a year or so, and it took me about a week just to get sound working :/ (which is longer than I hoped for). But, oh well, it's pretty nice.
I'm sure there are going to be haters for posting this as #3, with all the hardcore GANOO LOONIX fanboys out there. But, Ubuntu is one of the easiest distros to use. Everything that's essential is already installed and configured, there is no work required; but, because of this, it tends to be a bit resource heavy. I used unetbootin so I could use it on a live flashdrive on my netbook. I tend to just use it for aircrack-ng whenever I'm away from home ;)
God, I hate Gentoo. If I wanted to compile everything, I would have been just using LFS. Everyone who wants to get work actually done should avoid this. I don't want to waste half my life trying to get something to work in Gentoo. It feels like I'm going to have a brain aneurysm whenever I start Gentoo, just because of the misery that goes along with compiling. *sigh*
I know there are going to be GNU/Haters for this list, but please fee free to comment and voice your opinion :3