I've been on vacation for a few weeks. I've come back home and noticed this issue in the first game I played.
Description of Issue
In game, every 10 to 60 seconds (can't be sure), the game becomes unresponsive for about a half second. When the game becomes responsive again, I can see the ping indicator on the top right has become full (indicating a ping > 400). It gradually comes down to 32 after a few seconds.
This also appears in the loading screen (ping jumps from 32 to ~500 for one second and immediately begins dropping down).
Diagnostics and Investigation
1. I thought that the issue was with some program open on some machine on my network. I made sure all other devices were disconnected or turned off. Only my PC was on the network, which I verified with my router's admin page. The issue persists.
2. I checked my own machine, using NetBalancer. I blocked all programs except League of Legends and necessary Windows processes. I also ended all unnecessary processes via the Task Manager. The issue persists.
3. My computer was due for a reformat, so I did so. After a full reformatting, after which my computer is running like butter, the issue persists.
4. I used a different PC in my home. The issue persists.
5. I checked other games for connection issues. They had none.
6. I pinged some of Riot's North American servers, and found no packet loss or unusually high ping (< 40 consistently).
7. Made sure all my ports were forwarded (I'm DMZ on this LAN), and then tested using http://www.firebind.com/test/lol?start. Passed every single port.
The only possibility remaining is that there's an issue with my ISP. I have Comcast, and have had Comcast for well over a year. Although I'm not a fan of the company, I've had remarkably stable and high-quality service ever since I signed up. I've had no other detectable issues whatsoever, in any form. I'll try to borrow someone else's connection somehow, but I think it's clear that the issue isn't on my equipment or hardware.