Well, this issue was the one I have been noticing for many years now, over two rigs that I've had in that time, 4 different HDDs and 3 systems (Win7-10). Now I have an i5 2500k, 8 GB RAM, 570 GTX and two WD Drives (Blue 500GB via SATA3 and Green 2TB via SATA2->USB 3.0), and no matter where I put the ISO (except for the SDD), I get small hitches here and there when loading assets. If the disk parks its head in the meantime, they are much longer (a second or more as the disk spins up again). Now, with games on the SSD, is the first time that e.g. Xenoblade and RE1 Wii run perfectly for me without any audio/video pauses, except for your standard audio-stretch when the game goes under 100% speed (Xenoblade), but it's very rare with the latest optimizations - previously I had to overclock to ~4.4 GHz for Xenoblade to run mostly @100%, but now it runs just fine at stock clocks.
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Oh, and I gotta add that I had tried many, many builds of Dolphin over the years, both LLE with the DSP ROM and old/new HLE, and the end result was always the same. I have always thought that this was specific to GC/Wii emulation, since other disk-based systems don't do this in other emulators. And yes, my SMART is all fine.
And the game in which this issue was the most noticeable for me (besides Xenoblade, but Xenoblade is very demanding, so at first I thought that it was just because it's a demanding game) is Tatsunoko vs. Capcom, which does it very often, despite the fact that I can run it at 200% speed if I disable the limiter. I believe it's a split there between shader-compilation pauses and sound-effect-loading pauses, but for the first few fights I always have hitches when the CPU or I use individual attacks for the first time. It goes away after a few fights, but reappears when I boot the game again (the loading pauses; pre-compiled shaders remain there, I think, but they're very similar in time and are almost always accompanied by a new sound effect). If I use the Ishiiruka build AND move the ISO to my SSD - there are no pauses even on the very first boot. Now I just get slight visual glitches from async shader compilation, but they don't appear as often as (or are less noticeable than) asset-loading pauses.
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https://www.youtube.com/watch?v=hfVk5V9K4Lw <- the first result on YouTube for TvC on Dolphin, it uses an old build, but the behaviour it exhibits there is the same as in the latest builds (with pauses I described, first one @ 3:49 for the "select your heroes" voice, then for character voices as they are selected, then in battle when Megaman does his first attack, etc. - and the Megaman attack, I think, is a combination of shader compilation and asset loading).