A lot of it is the inconsistency on what routes lead and what routes don't. For example, an In route doesn't lead - it goes to the spot the QB is aiming for (the WR if accurate). Corner routes lead after the cut it seems, so they'll be apt to go out of bounds (before the cut, they seem to act like fly routes). Some crossing routes DO lead, like dig routes before a certain point, but after a certain point, they DON'T lead. RBs out of the backfield tend to demonstrate this, too. Arrow routes are especially annoying because of this, which is a shame because I love the arrow route in my HB-focused offense. Sometimes I fall into my "do it like a real QB" timing and the arrow route turns into some kind of whacked "reverse slant".
What I do on routes like that is pull opposite on the L stick when I make the throw.
So if it's a corner to the offense's left sideline and the WR is heading left towards the sideline, I'll pull the stick right (and perhaps either up or down depending on the position of the safety and corner). This will get the QB to adjust his target spot, letting the WR catch up to the ball.
Out routes seem to work like this too, especially considering you have to throw him AFTER the cut (unlike in real life where you deliver the ball before the cut towards the spot the WR should be at the end of the route - throw it with the WR still on his stem and you have more of a hitch/curl/stick route). I'd do the same thing, throw as soon after the cut I can, pulling towards the inside of the field with the L-stick.
Of course, you can (and probably should) use the L-stick on the "non-lead" routes, but you have an option there. On routes that lead, you probably will have to adjust, lest you chuck the ball out of the field of play or into the waiting arms of a DB.