I wish there had been more developed in the game then fight,kill/arrest,repeat. There are many different ways to do this but in the end that is the ultimate goal of any content. A couple instances say I am a stalker who is heavy in stealth and get a mission to recover an item, I can't just go sneak in and take the item I usually have to literally defeat all the opposition. Or say I am a Villain who gets a contract to steal money from a bank I can go break into the vault and take the money all day but until I fight the Hero and their minions it doesn't count. Maybe with the base building and player made missions they where headed in the direction to allow for more variety but as it is the goal is to fight and defeat opposition.
As to the original post: Any faction that is heavy mess or with the ability to totally negate your damage. I really hate tunnels especially if I have a large Hero/Villain (any more I just seem to make them all 4 feet tall).
Oh one last thing is pet collision detection particularly as a healer/support nothing like trying to use a targeted heal and being knocked around a corner or off a ledge totally blowing your line of sight.