Information overload. A friend mentioned that as part of the reason he scrapped a Savage Tide campaign at level 14; the casters were overwhelmed with choices that they had no way to quickly evaluate (along with the other issues mentioned previously). Probably more of an issue for newer players, or those not prone to reading rulebooks in their spare time.
See, here is another place I find 3.x has a problem for my playstyle and what my group finds enjoyable: mechanical system mastery. The group I game with are not dumb people at all- at our table, we have 3 PhDs (neuroscience, physics, and chemical engineering), a small business owner with an MBA, and a lady with a master's in counseling. We're also not novices to gaming- I've been playing or DMing for 25 years, and most of the group has been gaming at least 10 years, with the exception of the counselor, who has been gaming about 2 years. We've played a variety of systems, from D20/D&D 3.x, to Savage Worlds, WHFRP2, Dark Heresy, Kult, Call of Cthulhu, and NWoD.
For us, the only game that causes the degree of consternation and problems that have been mentioned ad nauseum in this thread was D&D 3.x. In order to really understand and use the system efficiently, you have to devote quite a bit of spare time to studying the books, the rules, and finding out combos that work together well (just as you said in your post). While I admit I'm the most hardcore of the gamers in my group (I often read RPG books before I go to bed for an hour or so), most of my players don't have the necessary amount of free time to invest to gain mechanical system mastery of a ruleset. When we played D&D 3.x, there was always confusion about how certain rules worked, what spells did, and the pace of the game slowed to a crawl as people looked stuff up. The other frustrating thing for my group is they tend to think "outside the box" and come up with inventive plans for problems or during combat. The 3.x DMG suggest +/-2 to a given situation just didn't cut it for us, and all of the players told me they felt constrained and restricted by the 3.x ruleset moreso than they did by any other game.
And yes, while you can "wing it" with 3.x, its by far a subpar solution to the problem of prep time. I tried this for a while, and I have a pretty good grasp of the 3.x rules. When I found was I ended up with decidedly swingy results- either the encounter was way too easy, or much to hard. 3.x never did provide any kind of clue as to what an appropriate AC is for a CR 10 monster, or what its saves should be like, or damage output, or special abilities, etc. And it didn't help much to look at monster in the MMs or other sources for guidelines- as has been seen over the last 8 years, CRs were often wildly off. In fact, there was not even a way to figure out what CR a beastie should be other than "eyeball it and then fun 4 or 5 fights with PCs of given levels, and see which situation results in them using 25% of their resources." When everything else was so codified in the 3.x system, this aspect of monster and NPC design was seriously flawed and not well thought out. In order to try to avoid this excessive randomness and swinginess, I'd often use classed NPCs as antagonists, both for balance reasons, and because it made more sense for my homebrew world. Again, you run into a statting nightmare in short order. And while I did "fudge" things here as well (like skipping skill points), you can't really fudge with saves, feats, class abilities, spells, and gear- the NPCs needed those things to even have a remote shot at challenging the party. In short order, I came to truly dread prepping a 3.x game.
In short, when running 3.x, winging it always felt like I was being restrained by the rules- the rules were so interconnected that fudging stuff ended up having repurcussions down the line IME, and I found it was better to simply stat up what I needed in an abbreviated format (ie, no skills, bare bones feats and spells, etc). Even then, the amount of work was excessive to achieve the result I wanted, and the players simply didn't enjoy the system due to it heavily encouraging rules mastery, especially at higher levels. We quit 3.x and moved on to other systems about 3 years ago that didn't require them to spend huge amounts of time outside the game planning and reading, and we had a lot more fun. I also found I could FULLY prepare encounters in Savage Worlds, WHFRP or NWoD by the rules in a fraction of the time I could in 3.x, and they were better balanced because the rules weren't as interconnected and intricate. I can fudge and make stuff up in these systems on the fly if I need to, and its nowhere near the ordeal it was in 3.x.
I have to agree with Hussar here- if the DM can fudge and make it work, thats showing the DM's strengths, not the system's. In fact, I'd argue if the DM feels he MUST fudge to prep his game, the system is actually a problem, either due to complexity or simple unweildiness. The 3.x system is both of these things IMO, and is remarkably rigid and hard to adapt to other situations or genres in this regard due to the rules interconnectedness, assumptions about power and magic levels, etc.
When 4e came out, we gave it a shot, and found it plays a lot better than 3.x- creative tactics during play and innovative ideas for dealing with problems is rewarded, while the "build" aspect of 3.x is mostly gone. 4e also gives me better guidelines about what works and doesn't at a given level, and reduces the interconnectedness of the rules to a managable level. As a DM who has work and research obligations, I found this advice is a lifesaver and makes prepping a game FUN for me again, while taking a fraction of the time 3.x did. So I ask you, if I'm getting the same or better results in game while doing a fraction of the work, why would I ever go back?