Part of MLP:FiM's appeal is in the anthropomorphic quality of it. It's enjoyable to watch cute and cuddly critters behave like humans, as evidenced by nearly every cat video ever.
With a humanized version of the same characters, you lose that appeal.
For example, just the simple fact the ponies are able to grasp small objects and function as a society that has no hands is intriguing, where something as simple as grabbing a stick...
...ends up adorable due to the sheer absurdity of it.
With humans, that special anthropomorphic appeal is lost, so a show like that cannot function on a basis of human characters doing human things. It's the equivalent of taking Shpongebob Squarepants and taking the show outside of the water. Suddenly all the puns and clever absurdities are null and void, and the show loses its appeal.
There's really only 2 ways that a humanized version of MLP will have some sort of appeal outside of being a very bland show.
1. The characters focus on more in-depth human characteristics such as love interests, extreme sports, etc. In the end you have a completely girly show.
2. The characters tie into the original show, but instead of ponies with human problems, they become humans with pony problems. In this case, it would be totally awesome, and I'd be all for it.
Unfortunately, most of the evidence points towards #1, so I see this completely doomed to fail.