So far the hardest game I've played has been the Sui Generis alpha/betas. The game uses procedural generation for animations (based upon physics) and not static animations (like most games) which means the enemy is unpredictable and you have to use realistic strategies and combat maneuvers to be victorious (feints, parries, ripostes, quick side/back steps, tripping, pinning an opponent to a wall, body checks, etc.). When a game uses static animations you know to counter move A with move B which makes opponents easy to predict and successfully counter. This is not the case in Sui Generis; you have to take into consideration momentum, timing, footwork, positioning, openings, balance, objects and the environment (tripping, getting weapons caught on a wall or other object, etc.), spacial awareness... so many possibilities and variables that every fight is truly unique and not repetitious.
The game also has the most advanced artificial intelligence I've ever seen which is capable of reacting properly to what is occurring around them both in and out of combat. This is no trivial thing since animations are procedurally generated and not the rock-paper-scissors hierarchy you see in games with static animations; everything is situational and the AI must take into consideration all the variables that a player does in order to react appropriately. The AI will also compare what gear you are wearing to what they are wearing in order to determine if they should attack or not. The AI will take advantage of attacks of opportunity (a weaker opponent might become more brave/aggressive if your back is turned or you are already engaged in combat, etc.).