Is there a difference in aerodynamic efficiency between single engine and twin engine airplanes? I've learned a lot of great information about aviation on this website. One insight I learned from a poster here is that, all else equal, for every doubling of engine power that you give an airplane, speeds increase by about 25%.

However you're not always comparing "all-else-equal" airplanes, for example sometimes I want to compare between a single engine airplane a twin engined airplane. Yes the second engine adds weight and drag, but the factor that I have the most trouble accounting for are the difference in aerodynamic requirements between the airplanes.

My understanding is that regulations require all single engine airplanes to have a stall speed of no greater than 61 knots, while a twin-engine plane could have an arbitrarily higher stall speed. The higher stall speed is directly correlated with higher aerodynamic efficiency, meaning that it should be able to achieve higher speeds than a single engine airplane of the same mass, drag, and power, would be able to achieve.

So I am looking for a simple rubric with which to be able to compare single and multi engine airplanes. I think that there are really two parts here: (1) identify realistic stall speeds for the multi-engine airplane and (2) formula for comparing top speeds between planes with X mass and drag and Y power and Z stall speeds.

Any ideas?
Your question really needs further bounding to be able to accurately answer.  I will discuss a few aspects.

First @ratchet freak is right on the money.  What engine mount are we talking about? A podded engine on the single and twin (or multi, since your one of your questions mentions multi) or some different configuration.

In the late 70's and early 80's there were a bunch of academic and not so academic papers and articles written on the topic.  Generally the focus was on the Cessna 336/337, O-2 and Defiant type aircraft.  There were also papers on a loss of engine scenario.  This got rekindled for the Voyager aircraft design and promotion.  The Voyager had a L/D of 27. And it was intended that one engine shut down in cruise flight.

The 61 knot rule for single engine is said to be influenced by crash survivability. I get that, but I will editorialize that several studies have shown that the chance of something bad happening with the loss of an engine is greater in a multi. 

Top speeds, stall speeds and mass (weight) are different parameters, subject to different trades.  Furthermore, putting this into the context of existing, production or some arbitrary subset of the universe makes your question hard to answer.

The real answer is that one can design for what you need.  You can have a very slow stall speed in a single or a multi, what would you like?  You can have a nice L/D with any number of engines, what would you like?  And you can haul lots of stuff, although there are not heavy singles around. But to generalize all three parameters, of these non-linear trades, into one rubric, would likely challenge even the most mathamatically talented aerodynamcists that I know.  If you can tighten the bounds on the problem, you might get a better answer.