My experience with the Relams is that I've been playing in them or DMing them since I started playing 2e (which was around 89, I think). Since I have had very little exposure to Greyhawk, I immediately adopted them as my "standard" campaign setting of choice unless I felt like doing something a little different. Since that time, I have read most if not all of the FR paperback novels, acquire certain 'key' 2e suppliments (notably the FR Atlas) and as many 3e books as I can get my hands on. Today, I will use FR if I want to run a typical D&D campaign because I am very familiar with the setting and it's various elements.
It's hard to say what I look for in a campaign setting. I guess it all depends on what kind of atmosphere I am trying to run. For your basic High-Fantasy D&D classic style, FR works fine for me but I also enjoy Scarred Lands because of its more low-magic, grittier feel. Planescape and Dark Sun I both enjoy because they are both alien and familiar at the same time. Planescape gives you an excuse to do really out-there things and running or playing in Dark Sun is an experience unto itself. I guess you could say that the "tone" and "mood" of a campaign setting are very important to me, since they help dictate how I'm going to run the game or play the character. Iron Kingdoms caught my fancy because of it's widespread integration of firearms and steam-technology, which is something I've always wanted to do with FR but didn't because it would change the "classic D&D feel" too much. Now I can run a game using those elements without having to reverse engineer an existing campaign world or create my own (which requires alot of hard work).
Unlike some people, I have no problem with FR being so "well-developed" through novels and suppliments and such. If anything, it gives the setting a sense of life, of motion and activity. Things happen there. There is always something going on, plots being hatched, organizations bidding for power, threats of war, and so on. Yes, I know you could have these things with other settings, but it is just so prevalent in FR because of all the work that's been done on it.
Another thing which turns of alot of people is the Elminster Factor. Major NPC's are abound in FR, so how can the PC's possibly shine when there are so many big-shots running around? Why don't they just take care of everything? Well, because they can't. The NPC's of FR add another layer of depth to the setting, they have duty and responsibilities to uphold. Yes, it can be difficult to run in FR without hearing some mention of Alustriel or Elminster or Drizzt, but they are really just figureheads. Mysterious names of great power that the PC's may never interact with, doing incomprehensible things. In short, they are window dressing. They play no part in the Big Picture whatsoever unless the DM wants them to. It's easy to run an entire campaign, from 1st to Epic levels, without ever running into or dealing with these NPC's beyond the occasional mention.
The conept of "culture mish-mash" has never bothered me. It gives me and my players a frame of reference in which to work and detail certain cultural idosyncracies. It also helps to make the Reams more "familiar" to those who aren't as comfortable with fantasy cultures that have no basis in real history.
There really isn't anything I particularly dislike about FR, since anything can be worked around. I also understand that the setting was meant to be High Fantasy and powerful, so I wouldn't try and run a low-magic, gritty mercenaries campaign there. Campaign settings are just tools, and you should always use the Right Tool for the Right Job.