So, let's look at the facts. In Fallout 1, super mutants were the henchmen of the big bad, The Master. After the defeat of The Master, the super mutant army dispersed, and subsequent Fallout games took the muties in one of three directions: fanatics trying to achieve The Master's vision (for example, Fallout: Brotherhood of Steel, and IIRC, Tactics), gentle giants just trying to get by (Fallout 2 and New Vegas), or in Fallout 3's case, brainless mooks pretty much only there to pose a threat to the player.

Yawn.

How about something new? Hell, I wouldn't even care if they were bad guys again, as long as it was done in an interesting way. Like, just off the top of my head, what if there was a faction of super mutants who were convinced that all humans were out to get them (which is pretty much true), and the only way they'll be safe is if they make all humans into super mutants? Turning them into a massive slaver army like Caesar's Legion, only giant, and immortal.

So, let me ask you guys: how can super mutants be made interesting again?

Well the FEV is gone so it's not like they can make more.