So once you beat the game and get all they extra goodies, you can't take those with you into another difficulty correct? So before I start the game (which I got for a steal of $25) I want to start on a good difficulty that would offer challenge the first time through, and not be a cake walk the second time through. 
Suggestions?  I hardly had any difficulty with RE5 on normal just for an indicator.

Dermm... The one above normal

the hardest of the hardiest types of hard

I played it on hard the first time and it seemed alright...made it seem like normal or anything lower would be just way too easy and no challenge at all.

I recommend starting at normal, then try to beat it on impossible, good luck!
You could always begin with hard, but if you don't have the patience and some gaming experience in games like this then you might get "stuck".
Meaning you don't have enough health or ammo to finish the mission you are currently on, which almost happened to me quite a few times on impossible mode.

Just do Normal first. Then if your sadistic you can do impossible.

If you want it to be challenging on the New Game+ playthrough, you should go with Hard rather than Normal.

I usually go for the hardest difficulty in videogames.

" Just do Normal first. Then if your sadistic you can do impossible. "

I would say it's quite hard to judge, because RE5 isn't all about survival anymore.
I hardly had any problem playing veteran difficulty with a new profile in RE5, but I found myself struggle with insufficient supply in Dead Space on hard.
I don't think DS on hard is harder than RE5 on veteran in terms of combat. However, the way in which the level structure and save system works in RE5 makes ammo and herbs never run out......
 So......How about start DS from easy to find out if its too easy for you, and slowly move up to harder difficulty? After all, this is a high-quality game that deserves to be played at least four times, right?

Just play on normal.

@lilarchie232:  Normal was an enjoyable difficulty. Hard wasn't too bad but you certainly have to watch your ammo a bit more carefully and play a bit smarter. Never tried impossible so not sure about that one, but I assume you really have to watch your ammo and health. From what you're looking for, I'd say try it on Hard. "

I found "hard" to be, well, too hard. When you run out of ammunition and credits at any point, you are pretty much boned. Unlike in "normal" mode, you can forget about collecting items in mid-fight to muddle through somehow, unless you consider Isaac a walking lunchbox.

If you want a fair challenge, I would definitely recommend playing on hard. Then play impossible mode (which actually isn't much different from hard) your second time. Hard just felt right to me for the first time through- reminded me of RE4's standard difficulty, at least the cube version (don't know if the other versions messed with the difficulty).

I would just start on normal because the first play though, your equipment and stuff l like guns are under powered you would need alot of ammo. I was constantly running out of ammo and had to sell two of my guns. Maybe on the second play through when everything is upgraded, then play it on a more difficult level.