A lot of guns are improvements on older or similar designs, not all new creations. And with military or LEO users, having to do the training on an all new weapons system is not always feasible, so evolutionary improvements (say from M16 to M4 to some piston type AR-15) may be better for some.
They often have issues for left handed shooters. Some eject the cases downwards or forward to fix this. From what the new Keltec RFB was described as, it sounded like they just end up dumping out the front if you point it downwards, which sounds lame but whatever.
I always hear nutnfancy talk about triggers on bullpup rifles being subpar most of the time, but I don't know why that is.
Also they seem like they would be slower to reload than a traditional layout but that's just my guess.