Truth be told, I've completed most of the challenges during normal play through without even realising it. There're so many different grind challenges, I can just ignore them as they pop up in the background. Others like the super mutant killing challenge gets a bit harder since the only time I get to kill a lot of them is when assaulting Black Mountain.
True, there are some challenges that just come out of nowhere and you raise your eyebrow and scratch your head thinking, "there's a challenge for that?". O.o
Still there are a handful of challenges that are actually worth pursuing as there are bonus perks associated with them.
At the very least, my "final build" character will be going for all the perk-related challenges. :thumbsup: