I'm not sure whether you want to change input variables or do runtime control. For input variables you can wrap EnergyPlus with a scripting language like Python, Ruby, etc, and using that to edit the input file, launch a run, and handle the results. The syntax I use is inspired by jEPlus where they denote values to be edited like @@variablename@@

I've posted a Python snippet for doing the IDF editing before. The link's here.

Launching a run is simple:

import subprocess

subprocess.call('"%s" "%s" "%s"' % ([path to RunEPlus.bat], [path to IDF or IMF], [path to EPW]))

And then finally for handling the results I highly recommend using pandas as a really good time series data processing library.

If you're talking about changing values during runtime you'll need to look into EMS or BCVTB.