anytime someone brings up one of the 5 biggies I can't help but cringe.
OOO
Midas Magic
MMM
Fcom
Better Open Cities
Hell, even Deadly reflexes made me weary until recently.
The problem is getting all of these guys to work together stabely. Then you have to worry about compatibility issues with these and other mods.
Currently I am running over 100 mods. Only 1 clothing mod, merged with all the race mods like BP and Demon Race. The rest are things such as Deadly Reflexes, Better Cities, Ruin Tails Tale, Tears of, Better interiors, Illumination, Kvach Rebuilt, Frostcraig Reborn, Blood Lines, Sirens Diception, all the official, SI, etc. All running perfectly, all at once.
While The thought of being able to go up against more and unique monsters make a weird little part inside of me smile, as a beggining modder I know I am not prepaired for them, and would much rather play with the other as mentioned without having to worry about toooooo many conflicts.
Oh, and the last biggy to be scared of is Unique Landscapes. Man does it limit you and force you to get alot of compatibility mods.

Hey, Here's a thought, Have you tried checking out your load order? Check out FCOM HELPER if you haven't already. The helper is awsome, and 90 some odd % accurate. I found only 1 mod out of place using it. Cleaned up alot of crash issues for me.