What are the mechanical differences between Doom and Descent from Fantasy Flight Games?
One significant difference that leads me to prefer Descent over DOOM is Ammo.
In DOOM, Ammo is "full of fail".  Ammo scarcity is a thematic element that happens to be implemented in an abstract way that is often flat out not fun.

The breadth of characters and skill and item combinations make Descent really come to life compared to the relatively lackluster variety in DOOM.  

The surge mechanism in Descent is really novel and can give you a lot of interesting tactical options in battles.  DOOM has no analogue.