First things first, please list out your command lines (copy-paste from the features tab in the launcher). Some are much more resource-intensive than others. For instance, I can tell you right off the bat to turn off -pcx32 if you're using it.
If it's happening in-mission (which I suspect it is, if it's interfering with playability) then the problem is almost certainly that something big is getting paged in to memory. The most common causes are sounds (helped by "preload mission game sounds" in the launcher), animated maps (the shockwave, shivan glowmaps, etc) or effects firing off at a certain time. If you can link the slowdowns to sounds playing, to weapons firing, or to ships arriving, that might help clarify how to better optimize your performance.
Unfortunately, the MediaVPs are really targeted at a high-end machine, so people with less ( <1GB Ram, <128MB graphics cards) are going to have performance issues with the graphics set you're looking at.