Always better to have more speakers. Whether or not you wire in series or parallel depends on what the speakers are able to handle.
Railpro outputs 1 watt of power to a single speaker. Wiring in series will present the Railpro amp with a 16 ohm load, it will decrease the output to the speakers to 0.5 watts (useful for speakers who's max watt rating is lower than 1 watt). Wiring in parallel will present the Railpro amp with a 4 ohm load, increasing the output to 2 watts.
Parallel tends to be louder, but I almost always wire mine in series because I'm not looking for massive volume. I'd prefer to keep the sounds relatively low and avoid overdriving the speakers (I use "sugar cube" type speakers with a max rating of 1 watt).
I have a MTH ES44 and found that using speakers designed for the factory mounts was less than ideal. I ended up taking them out and replacing them with two sugar cube speaker assemblies inside the fuel tank cut outs. It sounds much better.
-Kevin
