I guess "24" would have to get a mention because at the time it was unique and pretty groundbreaking. I wonder whether I should go back and watch them but I suspect they haven't aged well.
I think Breaking Bad was obviously fantastic as it built characters really well and allowed you to sympathise with a criminal life and all the baggage that comes with managing it and family.
I was thinking Breaking Bad, then I realised that the drug-dealing anti-hero had already been done in Weeds

More recently, Bojack Horseman has really pushed the envelope. The shallowness and loneliness of 'success', among other despairs of life (the ultimate lie of striving for a 'dream' and the emptiness of achieving it). That human connection is the real 'dream', but it's not what we're sold.
Oh yes, Bojack is unique as hell in that respect!