Think of your substrate as two layers, with
different functions: an upper layer and a
lower layer.
The upper layer of substrate is usually formed of coarse
sand and gravel, without nutrients that might
leach into the water. Larger pebbles tend
to rise to the surface in time, like the
stones in a New England field; silty stuff
tends to get buried. Only continual stirring
could retain an unnaturally homogenized mix,
but I'd caution you that gravel vacuuming
should be minimal; if gravel vacuuming is
unavoidable, try not to go so deep that you
cloud the water. Besides avoiding nutrients
in the upper layer, you also want to avoid
Ca and Mg carbonates and stick with chemically
stable, fairly uncomplicated elements.
The lower layers of the substrate are going to vary according
to what you intend for the aquarium you're
establishing.