I use it with OmniFocus on my iPad. I haven't used GTD apart from this program, and think that it would be too much work without OmniFocus.
I like:
-The idea of getting things out of my mind and into an "inbox". This really helps to clear up what precious little brain space I have.
-Organizing my "to-do's" into projects and being able to look at the "next actions" of each project. This really helps me determine what I should do at any available time.
-With OmniFocus you can set contexts based on physical location for things that need to be done a certain places i.e. Grocery Store, computer, school, etc. Again this helps determine what I can do based on where I am.
-I really do like the idea of only putting things on the calendar that must be done at a specific time. Previously I would schedule every task and, as you can imagine, something would come up and my whole day would be off. Now I use the free blocks of time on my schedule to do next actions.
-I have also found that the system really falls apart when I don't do the "review" phase. Personally I do it once a week and decide which items are on hold, deleted altogether, or implemented. So if you are going to use GTD, don't forgo this part.
Like I said, I couldn't imagine using GTD without OmniFoucus. There are other application out there that do GTD, but this one has been the best.
Hopefully that helps.