Regarding the greyed out buttons.  There are two groups of buttons the one
on the left is for alignment and becomes ungreyed only when two or more
layers are selected (one of which may be the background).  The one on the
right is for distributing spacing between the objects and is becomes
ungreyed only when three or more layers are selected (none of which can be
the background).

Alignment is with respect to an imaginary bounding box that encompasses the
non-transparent areas of all the selected layers taken together.  You aren't
locked in to only aligning on the center of the canvas.   In essence, you
center on the geometric center of the bounding box.

Let's take that case of centering some objects in an off center box.
Create the box and the four objects on separate layers.   Select the four
layers with the objects and align them.  Then, leaving the layers selected,
drag them to the box and drop them where you desire them or when the smart
guides indicate they are centered in the box if that's what you want.  You
can distribute the space if you wish.

The bit with the backgound confused you.  That's just a trick to force
alignment on the entire canvas (the background has no transparancy, so the
bounding box is the canvas area).  You don't have to create a reference
layer for alignment.

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