Yeah it is pretty daunting. Obviously you don't have to actually do it without dying, since the game allows you to save anywhere you want as many times as you want, but it will take some patience to keep on loading the game up each time you die.
My first run through has been on Hard and to be honest it's not the most difficult game out there. I think once I've done Survivor then Hard with no Vita-Chambers should become possible. Survivor with no Vita-Chambers remains uncertain especially since the arrival of Resistance 2 will take all my attention.
And I'm supposed to be fitting in Dead Space and Far Cry 2 somewhere as well, I don't know where to find the time for all these games at the moment.