To use the in-game tweaks you have to first complete the story once, and then you are allowed to use the tweaks on that difficulty and lower. If you were to, for example, complete the game on Hard and try to use the tweaks on Crushing it wouldn't work, though there is a way around that I won't mention which allows you to do that. There's little point in me looking up the way as I've already 'd UC2.
PSN/Steam ID is Icaraeus / 2 PS3s - 60GB 1st Gen YLOD'd 7 years, | 120GB Slim, 22 Games + Ton of Extras / PS4 500GB + 8 Games/ $1200 SuperPC since Feb14
I wish these games [Uncharted 2 and 3] gave more reason to play the stellar online modes, other than severe amounts of DLC trophies. Only needing 2 Online related trophies to plat kind of gives no real reason to need to play online, kind of sad. Then again, needing to spend $30+ on DLC for UC3 seems a bit intense, as well. [Unless of course you got the GOTY edition - I only just got the PS+ edition which is a rip off lol]