The assassins and Hired Thugs never really bother me. I just deal with them and be on my way. Although a bunch of Hired thugs tried to attack me once right after me, Illireth and Whiterun's guards just killed that first dragon at the watchtower. Boy did they pick the wrong moment. I didn't have to lift a finger as the guards, hyped up on the adrenaline rush of just killing a dragon, slaughtered those hapless thugs in seconds.
When I'm playing a warrior-type character, I actually
appreciate them sometimes. Even my current character, who isn't a barbarian-type warrior but a skilled and disciplined ex-Legionnaire, gets a certain smug satisfaction from putting down the disorganised rabble of thugs, or dispatching the assassin who thought he could go toe-to-toe with a verteran soldier. And from a gameplay perspective, it's always nice to have a skill boost (here I go, devaluing lives in favour of skill metrics!).
It's when you're playing a mage or stealthy type that they become a problem, at least for me, as those types aren't really geared for direct confrontations - the stealthy types especially. It's even worse if they catch you at an early level. The thugs in particular, as they tend to give you a good hard smacking before you can get far enough away. And not in a good way!
