Main difference for me, is we know we are playing proper poker. almost all players have a strong sense of Position and wil 3-bet accordingly play the correct range of hands in the right manner.
And more than anything I wouldn't say I find it harder but its just adjusting your game and thinking alot more about the hands, as generally alot of players have a reason for making a play.
In the lower sit n go's there is quite a high amount of donkish play and people betting generally with the hope to take down the pot without a decent idea of whats going on around them.
Ofcourse there is alot more aggression and people wont fold as easily if your playing open.
The way I look at it the better the player or the bigger the stack, the more likely he is to be trying something on or doing something to accumalate more chips, I will Target this as much as possible, because they will keep firing to disguised weakness, and back down to a well represented hand.
I dont see any reason if you have a big enough bankroll you cant profit at these stakes, if your willing to focus on fewer tables and maximise observation etc, and have alot of skill when it comes to exploiting players