In the align environment, it treats A & B as $A$ ${}B$.
which means if you input
\begin{align*}
A & B \\
C & D
\edn{align*}
What it actually outputs is a tabular with four items like

That's how align works.
As for your question, the spacing is added only when there's something after it. If nothing is after the "=", no space would be added.
I've also figured out why they do not add {} in the first cell $A{}$ ${}B$. Consider A&=-B. If add {} in both cell, the spacing between the "=" and "-" would become bigger(space is added twice).
Also, "=" should be on the right-hand side, or the minus sign would be recognized as an binary operator, thus cause extra space between minus sign and B.
You can see none but the first one made the correct spacing.

In real life, the Relation sign is often followed by Ordinary, But to proceed with Ordinary/Binary/Operator. Thus, the author made suggestions "=" must on the right so that character after "=" could be classified (Ord/Bin/Op) correctly.
In our little example, only when the Rel is on the right can the TeX figured out the minus sign as Ordinary rather than a Binary.
As for your question, if you don't mind adjusting the spacing manually, you can use A={} & B. or you can use
A & = B \\
&\phantom{\;=\;}C
The \; is normally added by TeX automatcally.
&. Please, add an example of what you mean by "emulate multiline equations". For getting the space right, use&=. But also={}&can work. – egreg Jan 14 '12 at 11:46&\phantom{=}work as well? – celtschk Jan 14 '12 at 11:56\begin{align} a=&axy+b\\&+y\end{align}, but it gives the wrong spacing, as I argued. Both={}and&\phantom{=}seem to work, though. – Federico Poloni Jan 14 '12 at 22:36