This came up when I was playing Sir Knight's Pigs custom scenario. In this map you control Xanthicius, a large (2x2) figure. What I found was that, if there was an enemy on Xanthicius's north-by-north-east flank, as pictured below by the blue square, I was unable to click on it when targeting attacks. I had to turn Auto Target on in order to attack the pig at this position. The problem here is I think the same problem we have when trying to target a grid square beneath a figure when moving—when you mouse over a figure, that figure obscures everything behind/beneath it. And it just so happens that Xanth (and probably some other large figures) are so big as to completely obscure any figure directly behind them. I know this is probably a corner-case thing, because players don't usually control large monsters. But finding some way to allow manual targeting behind a large figure seems important for long-term extensibility.
A lot of things in the game could stand to be accessed by the keyboard. That said, this is probably something the devs might want to fix for mouse-users regardless.
We've had some things like this before, because however much this may be true: . . . it is still challenging for players to target around large enemy-controlled figures, like this Goblin Hulk. I bumped into the here-piggy-piggy example in playtesting, and was frustrated that the Xanthicius figure refused to fade to allow me to click behind it. But I too would rather they come up with a mouse-first solution (like fading figures more readily) than focus on keyboard solutions. Perhaps a keyboard-triggered forced-fade would be enough. As I brought up in that old thread (though I can't find the references anymore), the devs don't want the more involved solution of keyboard-only gameplay, because clicking on the board enforces principles of positioning that are essential to understanding the game.