First, let me say I'm a long time fan of Nintendo, but not enough of a fanboy to have owned the N64 or Virtual Boy. Although I still have my GC game collection gathering dust on a shelf. That out of the way, I will get to the heart of it:

Porting Games:

With 8GB's of flash storage, HD gaming will face a serious bottleneck. I know the Xbox360 worked around this quite nicely, but this is the next-next generation and you can bet Wii U will be the only new system without 60GB+ HDD.

Wii U could fall into the trap of only getting token use made of the new touchscreen due to hurried multi-platform software launches.

Controller Price:

Let's assume the Wii U only comes with a single controller/screen. How much will a second one cost? $89? $99? That price point would seem to be the absolute highest Nintendo could get away with, and it's way too expensive.

The Wii:

So many casual gamers jumped on the Wii bandwagon. After mastering Wii Sports, 75% completely lost interest. How will Nintendo lure those same buyers out again with the addition of a hand-held screen?