Belethor in Whiterun is an arsehole
Lol, his voice annoyed me so I sneaked into his house at night and stole absolutely everything (even the things not worth any money), pickpocketed him and that other guy living there (including their clothes) and spent the rest of the game laughing every time I walked into his shop and found him wearing nothing but a loincloth.
Assassination is much too easy compared to a lifetime of humiliation and nakedness in my book.
As far as assassinations go though, I kill every vigilant of Stendarr and every Thalmor justiciar I come across. No exceptions.