Handling - good. It was great even coated with blood and fat. The grip could be a little longer for me, the curve at the end feels like it crowds my fingers but I have big hands. I've heard other people complain about the point at the end of the curve but it didn't bother me. The lockback design works great for me, even though I'm used to liner locks. The grooves in the top of the blade are just sharp enough to grab your thumb but not end up irritating it. I do think it sits too high in a pocket when using the clip, but that's no big deal really. It's lighter than I thought it would be, which is a big plus. The scales have a rather agressive checkering pattern, it's not really deep but it grabs your fingers pretty well.
Edge retention - Really good. I'd say the only knife I have that's better is a custom made by Gene Ingram. My uncle was using a decent carbon steel knife and he ended up giving up on it and using the manix instead. We started with 2 hanging does and we had 65 pounds of ground venison (plus the loin chops, yum!) when we were done, so there was quite a bit of cutting. I stropped it a bit Sunday night and it's back to extremely sharp, it easily pops the hair off my arm. I had to sharpen the Ingram but I did use it quite a bit more. The blade on it is D2. It also has a bit of a stain now.
Fatigue - Well, I hope I covered that pretty well above. I didn't have any problems with fatigue. I used it for almost an hour straight at one point in a lot of different positions and no problem there.
All together, it's just a great knife for what I wanted out of it. I wanted a decent sized blade that would be a good folding hunter and general outdoors knife. If that's what you're after, I'd say go for it.