I have a 6.4, and ran the first 30k stock, and it was a dog. I was really quite disappointed in it. Then...the dpf came off... and on went spartan and 4" flo pro exhaust, and never looked back.
It runs awesome now, i don't see anywhere near 20-25mpg like some guys are claiming, i think they are looking at there lie o meter, and not hand calculating. For some reason the spartan, makes the dash mpg's read anywhere from 2-3 mpgs high, so if it says 20 you are actually getting 17mpg. All in all i am thoroughly happy with what it did for my truck, still thinking about the egr delete. You really need to do that too if you want a bullet proof setup.
As far as the manual goes, i think it will handle it, but the clutch is the weak point. Definately plan on a new clutch right away, if you are gonna run the high HP tunes, which are the ones that get the best MPG's. The autos handle the big power just fine, and no clutch thingy!
My next truck may be another 6.4L with this setup as opposed to the new 6.7L with the price tags on the new ones!! If your gonna leave it stock though, i would go with the 6.7L for better mpg's, etc..