I found various parts difficult and others just annoying but only one particular part stands out til this very moment (I finished it in July-Aug 2010). The part where you investigate the Collector Ship, the very first part with the flying platforms. Harbinger shows up with some drones and 2 Scions. Man, with Harbinger's gung ho mentality (not to mention his Singularity-esque attack that disorients and sets Shepard back), the drones and Scions' Shockwave I was left frustrated with this part. I actually ended up rage quitting and didn't touch the game for a whole week but then I went back and finally beat it.
There are a couple of other spots I found tough like the two Praetorians you fight on Horizon and in the Collector Ship and Archangel's recruitment mission but that above bit was by far the toughest.
Here's a clip of it (this guy makes it look easy mainly because he has The Widow but believe me it IS on Insanity)
EDIT: Three more parts I found tough - Mordin's recruitment mission, turning on the valves. There are Vorchas shooting rockets from a ledge while Pyros and Krogan charge at you - fuck. The second one is getting the Reaper IFF, Husks and Abominations do quite some damage in big crowds but then you got Scions closing in too, just brutal. Last bit, Zaeed's loyalty. Big room, lots of cover but kind of boxed in at same time. Blue Suns mercs mostly Turians with shotguns, some pyros too and a big mech. Ugh, it took me a while it has to be said.
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