Prelude:
I have a laptop that has far beyond the necessary specs needed to run this game, however I was getting terrible stuttering throughout it. My computer runs an AMD A8 series processor with a dedicated Radeon HD 7680 video card and 6 GB of ram. The issue is my HDD. It's a crappy "green" HDD that's supposed to keep the computer from using up excess amounts of power by slowing the rpm (5400 yuck). Because Diablo 3 doesn't utilize ram very well and instead reads the entire game off the hard drive, games took forever to load and even when they did, I had horrible performance. On max resolution and lowest possible settings, I would get between 11 and 30 fps. Now I get a constant 55-60 on max.

How I did it:
It was a simple fix. I had a spare USB flash drive laying around so I reformatted it to NTFS and moved my D3 folder to it. That's it. I open the flash drive directory and run the D3 launcher. It starts about 6 seconds slower, but the performance gain is incredible. Plus, I have portable D3!
Note: You need at least 16 GB free on the flash drive.

Why it works:
Like I said before, D3 poorly utilizes the available ram on a computer and instead reads from your continuous moving HDD. The flash drive has no moving parts and is completely dependent on your read speed of the drive and device.

Another way to do this would to invest in a SSD, but that's a lot of money. This is a cheap, easy fix that allows portable Diablo and no need to work with Ramdisk.