+1 to issue with invisible items.
In general this never bothered me, I guess that's because the first thing you're supposed to do in an RPG is become familiar with the user interface, make sure you understand what all the icons on the screen mean and what use they have. You can't expect everyone to think this way though, will it really be so hard to autoplace items to backpack?
Game isn't hard, at least for the old school gamers. It just takes some time to understand the interface, as SaikoDeMoN said.
Either way it doesn't matter that much, the player will eventually notice the backpack anyway.
According to my observations, players don't understand it quickly.
It's pretty funny - watch how 3-4 ppl party kill a mob, got an item drop, click on it several times and then continue killing mobs, leaving item on the ground.
Well, sometimes player understands that he must uneqiup current item to take a new one, but doesn't place old into F2 backpack.
In my memory, only one player guessed to use F2 backpack without any advices.
Maybe I was just unlucky with random parties, who knows?
I suppose "quality" of players lowered nowadays. You know, almost all AAA titles are very casual. So players think that game will lead them through the starting location with tutorials, fancy pop ups and other things that make newbie's life easy. Maybe that's why they rush into the action and don't waste time on the interface.
Also, some players have "partial blindness" on the error messages if they don't appear at their focus point (i.e. over clicked item). So it looks like: "Why I click on the item and it doesn't picked up? Well maybe try with another one.", "Oh, nice dagger, and I'm a thief, take it, TAKE IT! Why it doesn't pick up? WTF, this map is broken! [MENU] -> [QUIT]".
And don't forget about "herd instincts" that don't let players to just stop and sort things out. "Everybody runs and kills mobs, and I will run", "Everybody ignore this item, and I will just leave it on the ground".
In addition, players nowadays can not "fight" with difficulties. "Oh no! My character died! And I must wait 1 minute before ressurection?! WTF, why I must wasting my time?! [MENU] -> [QUIT]" (well, in Dota players can wait much more time, but this happens only in the late game, so player understand why he must wait so long)
In any case, I described it all earlier in thread about newbie friendliness.
tl;dr: Gaias can attract more players if you make some things easier / more understandable (at least for newbies), but overall "player's skill" will be lowered.
Or you can keep everything as is, because Gaias already have nice experienced community.
So community will help newbies to understand some hard things and tell about interesting things in lategame (you know, first levels show only around 20%-30% of game possibilities).
But keep in mind that experienced players mostly active only after content updates, and that they will try to play with other experienced players and with high leveled characters.
P.S. In any case, my arguments are quite subjective and based on my thoughts, not the real gamedesign experience. So I will not push this kind of ideas more

.