Three performance-related issues in Diablo III seem to be centered around using the Vsync setting in the in-game video options, disk asset loading stutters, and a possible overheating issue.
Vsync: Vsync stuttering is normally caused by a machine being unable to maintain 60fps, falling behind and then alternating between 30fps and 60fps. When this is the cause, the player may want to limit the frame rate to 30fps, or reduce system and graphical settings. Ongoing optimizations by the developers will also help on this front.
Disk loading stutters: We're working on the disk asset loading stutters as well. In an upcoming patch, some of the prefetching in the game is being changed which should help with the stuttering.
Overheating: There are some people having what appear to be video driver resets leading to long pauses as Diablo III reloads assets and then resumes playing. We're working to reproduce the issue internally. For now, we believe it could be due to the video card (GPU) overheating. Many users have addressed this on their own by limiting the frame rate and underclocking their GPUs.
The developers are making incremental improvements to address these issues. These will be rolled out across future patches.
