I have a lot of different key setups for different game genres, and on top of that, my typing style is a bit "slurred" (meaning I tend to err on the side of holding keys longer, so I'm often still holding previous key(s) while pressing the next). As a result, 2KRO tends to be a problem for me, though some 2KRO designs are much worse than others.
My MicroConnectors D07-135, for instance, had big issues in FPS, because it didn't like W + E + Space (forward-sprint-jump). I-Rocks KR-6260, a dome keyboard with a "gaming optimized matrix", would reliably block out the "r" in "keyboard" during fast typing. I don't use my Model M enough to recall exactly what blocks and what doesn't, but I remember hitting the limit once or twice.
Now with 6KRO, I find that it's vastly less common to run into issues. It's almost always fine for recent games, where the mouse is used as a main form of input, but for older games and keyboard piano, occasional trouble can occur. And of course, it's always nice to have immunity to my old trick for winning at games with multiple players at the same computer: wait for a critical moment, then slap the nearest available section of the keyboard with your whole hand to block out the other guy's input.