In some cases you can, with some weird side effects (riven, broken sword) but in many cases you can't, and have to duplicate files (because the game doesn't go down the hierarchy of cd 'readers' so extracting the files into the native filesystem and doing 2 mounts in dosbox is useless).
For instance i can do the 'this is a cd *and* the install dir merge trick with broken sword, but can't with RAMA or Versaills 1685 or discworld 2, World of Xeen (cd), other games i forget. The number of games in these circumstances is admittedly small, but i think they're rather important, since they're large cd games, engine re-implementations categorically refuse to add a ISO/CUE/BIN parser/reader and scummvm is adding new engines at a fast clip (and new ones are appearing like openlara).
For instance it would only take scummvm adding a 'Under a Killing Moon' engine to waste - slightly less than because or ECC - 2.3 gb in duplication if you wanted both versions running)