Depends on just how different the version of the d20 System being used is, I find.
As there are so many similar game with the whole "VP/WP"-style system w/variant combat out there, it gets very easy to confuse particular rules, much more so than you suggest, I think.
Confusing 2E and 3E certainly happened, but even when one did, I at least often realised, and mostly it was simply due to assuming the 3E rules were the same.
Whereas confusing original WotC Star Wars, Star Wars Revised, Traveller T20, and Spycraft can get a lot more hectic (not to mention d20 Modern or d20 CoC possibly sticking an oar in!). I mean, I can you remember exactly which of those system armour adds a DR, and whether that DR applies against both VP and WP-style damage, or only against VP? How many points does Toughness add? Which does it add them to? What counts as "Helpless", exactly? What benefits does that give you? And so on. Many of the games have slightly changed Feats, too, which can be confusing. "So I get a +2 on AC from this Feat, now, not +1 vs only one person?" "No, that's the other game...", "We don't have AoOs in this game, right?" "I think we do... But was that the other game?", "How much damage does a .45 autopistol do?" "2d6. Er, or 1d10, or possibly 1d8, or 2d6+1. Hmmm." and so on.
Some parts of the game stay more or less constant, but in general these were the easiest parts to remember, the skills, and the like. Even then, though, unless you use character sheets during generation (rather than a pad), you may find players putting points in skills that don't exist in that game.
In the end, you can always look it up, but that *does* remove the utility, because you could do that anyway! It's not having to that was the main benefit.
I mean, learning the *basics* of system is not hard. It really isn't. Even Rolemaster's *basics* were simple. d20 generally means you don't have to learn the basics, it will be d20 + a number vs another, fixed, number. That only saves you half an hour at best, though, I would suggest. Certainly lowers the "apprehension" barrier for new players, but that's because they don't know better.
Learning the intricacies of a system can take much, much longer, often, given how complex 3E-style combat rules can be, as long as learning an entire simple game system.
It's not like I'm some "n00b" who has been playing RPGs for a few weeks, with my bro, I've owned and/or read, and in many cases played, perhaps 80-90% of the RPGs out there since 1988, and I pick up most rules very easily, but the intricacies of a system *ALWAYS* take time to learn, and if you don't go through a non-D&D-based d20 book thoroughly, you will almost certainly be playing it "wrong" in some way, because there are so many minor variations and subtle differences.
So yes, I'm afraid the d20 system's strength can, at times, be it's weakness. This could be argued to be the fault of developers, not the system itself, but that's really immaterial, because that's how it is, for now.
