You have to complete the game once to earn the right to use this difficulty. If you took the time to get the
trophy, you should have been able to get the pretty close to the best weapons and armor on your first playthrough. The weapons come back once you earn Spectre, letting you assign them to new squad members. Completing this trophy allows you to start Insanity for the third playthrough.
I recommend making use of the ability to hide the front end of the Mako behind cover and blast big things, like Armatures, safely without fear of reprisal. Staying in cover inside buildings is not really an option, most enemies will come after you. That being said, many buildings have somewhat safe areas where you can save your game and just sit and regenerate your shields and health (I definitely recommend you equip both shield and medical upgrades on everyone.)
I don't suggest doing the Rogue AI assignment if you already have the specialization, it increases in difficulty a lot. Every thing else is doable, though I found myself taking out missile silos on foot during the Bring Down The Sky DLC. It's a bit challenging, but easier than keeping the Mako alive with missiles coming toward you from multiple directions.