RAGE

First things first: Difficulty achievements are stackable! Woohoo!

There isn't too much difference between the different difficulties except that you will take more damage from enemies. There will still be the same amount of enemies on every difficulty, however, and you will still deal the same amount of damage to them.

Overall I would rate the campaign difficulty a 4.5/10. If you have already played through this game once and are now attempting it on a harder difficulty then you will know where the hard parts are (few though they are) and you will know when to save in case of a catastrophic failure. If this is your first playthrough, however, then here is my best advice:

Save often!
You might as well save as much as possible since you have the option to. Big fights are pretty easy to see coming as they often take place in large, open areas, so definitely save before moving on to a large battle.

Use Wingsticks & Sentry Bots!
I always make sure to have a full inventory of Wingsticks and I spam them on enemies far more frequently than I use bullets. Aim for the head and you will most likely get a 1 hit kill even on some of the tougher enemies. You can buy Wingsticks from any vendor after you have unlocked them by talking to Loosum Hagar toward the beginning of the game.

Sentry Bots are not only adorable, but when it comes to weaker enemies such as mutants they will pretty much do the entire fight for you and you won't have to lift a finger. They are also very helpful against boss type enemies because they make a great distraction for anyone in the room letting you focus your full attention on the boss. You can have 2 out at a time. You can buy the parts to build them from any vendor.

That should be enough to give you an idea of how to play this game, and the rest is up to you. The best part of Rage is exploration, so I don't want to tell you too much of what to do. I will give you a few more resources, though, to help you with various parts of the game if you're interested. Thanks for using my achievement guide!

Full Walkthrough:
http://rage.wikia.com/wiki/RAGE_Walkthrough

Obsessive Compulsive Achievement (includes Jumper, It's Good!, Gotta Have 'Em All, & Master Chef:
http://rage.wikia.com/wiki/Obsessive_Compulsive