Please help me figure this out...

I have a nifty fifty that I am unable to effectively use on my 5Dm2. I can take one photo with it then the viewfinder goes black. I am able to switch to live view and manual focus, but after the first pic that in the only way I can shoot.

What do you think is up?

Sounds like its causing a mirror lockup of some sort

That is what I thought too, but why and how do I avoid it? I have two other great lenses that have no issues, but I really wanted to play with this lens and see how it did on FF. I am very concerned that if it happens with this lens it will happen with others later.

Please tell us which nifty fifty? -- some, such as adapted M42 Asahi Takumar, the 5D mirror hits when lens is focused at infinity, but not when focused closer.

Canon 50mm f/1.8 II

Is camera battery almost discharged? If not the lens has a problem...could be as simple as dirty electrical contacts. try cleaning contacts with q-tip dipped in alcohol; they should be shiny like polished brass.

can't imagine a Canon Nifty causing mirror interference unless it's been damaged (check rear of lens to see if there's any scuff marks maybe?)
Does the problem happen if you're shooting in Av mode and have selected f/1.8? just wondering if it could be sticking aperture blades...

The lens is in great condition. It originally lived either on my xti or when not on that body, it was tucked away in a padded case. I inspected it and there is no damage to it. The contacts are bright and shine. It has never been dropped or even bumped. It was purchased new. It still works without issues on the xti.

I shoot in manual. I tried it with several different f stops. Each time the same thing happened. First shot works then after that the viewfinder is black.

So strange....

Very odd situation. Have you tried taking the battery out of the 5D, as well as the backup battery? Or reset to factory settings? I can't think of what would fix it because it's never happened to me but most people seem to suggest that for problems like this. Hope it gets sorted.

hmmm, well if the mirror is hitting back of lens, which gives the same symptoms...sorry, mine is not handy -- does the rear of the lens move into the lens body when the lens is focused close? I can't remember -- anyway if the rear portion of the lens does move into the body when lens is close focused, the mirror should not hit it, if mirror hit is the problem. Try it again with lens manually focused for close up. If the problem persists, then mirror hitting is not the cause. I'd next call canon support...