What Phantombeta is saying is correct. I've run GzDoom in a RAMdrive, many times faster than any SSD since it uses volatile memory (my 32GB of DDR4), and it made not much difference in speed.
I also tried many techniques to reduce the size of my PNG's. The GPU would still run out of memory and the stuttering in-game was horrendous due to being unable to pre-cache. It reads each pixel decompressed as data, regardless of the detail in your image.
So what I did was take my 50 frames per enemy and reduced it to 1024x1024 instead of 2048x2048 and it was fine (Mostly, LOL). I even experimented with a compress-less PK3 (zip) file.
The culprit evil fiend
was the PNG files themselves.
The bottleneck is the decompression and even the GPU memory limit possibly. Yes, I realize some of my issue was different than the current one, but it proves the point of decompression.