At least a few other people said
Very Hard...The only part of FO3 that was remotely difficult was the Point Lookout DLC because of the "armor ignoring 35 dmg every hit or w/e it was" that svcked... well that and they had a lot of life... other than that though...
I think it depends more so on how well you plan to build your character, I always went for Crit perks, high luck, and sneaking attacks. But if you wear power armor and go in with a minigun I bet the game is a lot different balance wise.
Sneak Attack Crits are Over-Powered. And the ever so awesome, nade reverse pickpocket insta-kills