I think it would be cool if there was a group of assassins or something out to get you, and they could appear at any time and attack you. You'd be safe in a sanctuary, but anywhere else in the open world would be fair game. Some may not like it, but I think those who want the open world to be a little more dangerous would enjoy it. The assassins could be synced to your item level to make each encounter more of a challenge. And there could be achievements and rewards for fighting off X number of assassination attempts.