In the mission where you infiltrate the White Box company, after you kill the guard by the front car lot, infiltrate the building. When you first see the room, you can either climb up the pipe and throw an object (frag grenade, proximity mine, remote mine, sticky cam, or EMP grenade) into the room. Even under the Realistic difficulty setting, the most the AI can do is shout and raise their guns, provided you have upgraded each gadget to the maximum. This room provides many ways to get and complete any challenge, except for most of the Splinter Cell challenge group. Also, this can be repeated by reverting to last checkpoint an unlimited amount of times.
Use your grenades when you need to clear out groups of enemies that are hiding in cover. Make sure you are a safe distance away when they explode.
Save ammo and time by aiming for the head to get one-shot kills.
Iron Sights Mode
When you are in perilous situations switch to Iron Sights mode so your aim automatically snaps onto the nearest enemy.
Whenever possible use melee attacks as these will charge up the M&E skill.