I noticed this in play, rather than spotting it in the rules, but as it's a head-scratcher that exists as a consequence of the rules, I suppose it fits here.
When trying to prevent an opponent from attacking a more vulnerable party member or NPC (or even just trying to stop them from reaching a specific location), standing between the attacker and the target is less effective than standing on the attacker's far side.
We've been playing on a grid (we intended to try TotM but habits die hard and we've also got an active 4E campaign running), where the issue is more apparent, but it could manifest without it depending on how precise your group tracks positioning.
There are two squares (ten feet) separating the attacker from the target. Instinct (mine, anyway) says the defender (not in the 4E role sense, just in the general sense) should position themself in one of those squares.
However, if they pick the one closest to the target, the attacker is free to approach without provoking an attack, and may in fact be able (depending on how open the battlefield is) move around freely enough as to be in position to attack the target while leaving the defender needing to move again in order to reach them.
If they pick the one closer to the attacker, the attacker is still able to move within the defender's reach without reprisal, circling around to a position where they can attack the target. The defender is slightly better off here, as the attacker hasn't moved out of their reach, but the target is no better off.
But if the defender positions themself on the far side of the attacker such that the attacker is within their reach, the attacker cannot approach the target without provoking an attack from the defender. The only places they can move without reprisal at best gain them no ground and at worst (for them) take them further away.
It's entirely possible that forthcoming tactical modules address this, but for anyone not using those this situation will remain: standing between a melee attacker and their target is a less effective place to defend from than one might expect.