"me" serendiptiy

I am answering this only because I just happened to review a chapter
on the very question that you raised.

>First of all, what is the most reliable way of determining whether the mood
>of the verb is imperative or indicative when the endings are the same?

The only way is by context. That is, what seems to best fit the context
of the text at hand.

As to your question regarding the "rule" whether the present imperative is
always used with "me" in prohibitions to prohibit the CONTINUENCE of an
action, I can only say "never say never." :-) It seems that there is always an
exception to a rule. But yes, as a general rule, the above is true. I have not 
this enough to specify any exceptions.

Examples of its use can be found in Mt. 6:19 and 1 Jn. 2:15.
Best wishes.

(Source that I just happened to be reviewing: 
An Introductory Grammar of New Testament Greek, by Paul L. Kaufman, pg. 123.
(Kaufman has been teaching Greek for over 25 year).