Heh, think of it as an encouragement - you can have your hundreds of mods and play them too.
The biggest obstacle, and what nearly made me give up, was the "file thrashing" that occurs if having 375-400 plugins and BSAs in the Data folder. Took me a while to figure that one out. The key for me was to use TES4EDIT to esnure there were no obvious (conflicting scripts are hard to catch) conflicts whatsoever and to solve the conflicts by making my own custom patch. TES4EDIT is a tremendously useful tool and I'd go so far as to say that learning to use it is a prerequiste if you want a stable game with more than 100 mods.
I remember that "file thrashing" craziness from about a year ago. The setup waiting for me at home is 380+ plugins strong, but I've merged it down to ~260 with ~205 active. I need to add one more plugin to that, but it is otherwise fairly set. Right now, my merged Animations plugin only has two mods, so I did not have to deal with the script conflict issue except for Adonnay's Classic Weaponry and Elven Weaponry mods' overlap. That was a few minutes TES4Edit patch though.
The PyFFI-Optimization of all of the major mods that I am using, now that took hours. I did PyFFI-optimizations for three or four days. It took an entire day to organize and tweak my BAIN folder (after a fresh install.) I spent the first two days of the process grabbing updates, of course. Reading to catch up on the forums and updates occured over the course of the six-day preparation, and I am still not done. It did not help that I meanwhile was trying to complete the building of a new computer for my cousin, during which the computer through at me every error I had not heard of, the worst being Windows 7 ignoring the stinking HDD!!
...okay no more ranting, sorry.