I'm doing this now and loving it. I had played thirty or so hours of the game leading up to it, when I started to feel a bit bored with the easiness (and this was with some mods installed to make things harder. As an aside, I enjoyed Skyrim with the Requiem mod, and STALKER CoP with the MISERY mod (although that latter one is not really for playing Iron Man mode.
If I know I can just quick-reload anytime I die, it is very very hard to avoid doing things which I would never actually do as a real person. For example, launching a single-man assault on the powder gangers prison base because... I'm a hero? It calls your morality in question as a result. Sure, it's easy to be a hero when you haven't really put anything on the line, but what about when your death means starting again from the beginning? How moral will you be then?
This has been interesting to find out. My character now wants to live. And morality comes after that. I still play as a typically good person, but I'm not hero. I don't stick my neck out, I look for opportunities. A nibble here. A bite there. I'm certainly not above stealing things when I can get away with it, and damn the Karma. This has made the game better then when I was trying to be more of a Lawful Good kind of guy too.
Currently I've made it to Vegas, and done a few basic quests around the place. I'm set up in the Atomic Wrangler with my dog guarding the door, and Veronica as the mobile workshop inside. Kind of feels nicer than being in the 38. I'm not yet at level 10, so I'm still pretty weak, but with some Mark 2 combat armor, a lever action shotgun and a hunting rifle outfitted with a scope, I'm just starting to stretch from being a fetch-it guy to being a low level hunter/thug. I've had a few close brushes with death. Once was when I opened a door in a building outside of vegas, and there was a string of mines just next to me. I managed to back away in time to only have my legs crippled, and I crawled my ass to the doctors nearby. Another time was when I stuck my head into the H and H tools facility, and got nearly blasted to bits by a lazer wielding bot. There was also a brush with some bandits which I ended by throwing a hand-made tin can grenade for maximum effect. Then of course it was pretty scary when I "met" Benny in his apartment, without knowing exactly what would go down (never having got that far before). I really had to steel my nerves a bit for that one. But I survived it pretty good with my 90 in guns and a few quick head shots with my L22.
Great way to play. Loving the game even more, and its a nice game as it is. This with good mods for hard play brings it closer to pure bliss. Also, the smoking mod. Damn right I light up a cigar whenever I survive a particularly nasty fight.