When Genosha was attacked by Sentinels, it had become a large population centre for mutantkind, with sixteen million residents killed in the attack. I assume there were at least a few million who didn't live there. What is the largest number of mutants living on Earth there ever was at one time?
In New X-Men #116, immediately following the Genosha attack, we actually see an answer to this:
Genosha's population was about 16 million, and the news reports that it contained "over half" of the mutant population, which means, at most the accepted world estimate was 32 million. I've seen numerous reports that the actual world population, pre-Genosha-attack, was around 30 million (the news report said over half, after all, not exactly half), although I can't find a source of it (most articles which cite the figure cite New X-Men #115, and the only number I could find there was the population of Genosha itself). Still, it's a good estimate.
Was this the largest number of mutants living on Earth? Signs point to yes. This occurred during the Morrison run, and in the first issue of that, both Beast and Xavier comment on how there are so many more mutants now (Beast specifically refers to it as a mutant baby boom). Morrison's run was also the first to include "Mutant Town" (a neighborhood in New York City with a majority mutant population) and widely expanded the school from what we knew. It's very possible that the X-Men were ahead of the news reports, and so they knew of more mutants and the "over half" estimation by the media was an overly-high percentage based on a lowball count of the overall mutant population, but at this point that's speculation.
Not too long after the Morrison run, of course, we had the House of M event, which ended in Decimation, in which the vast majority of mutants became normal humans. At this point, the mutant population of the world went down to the hundreds (although sources were not consistent on what percentage were wiped out or how many remained and some even conflict the pre-Genosha estimates) and it looked for a time that no mutants would ever appear again. Although that gloom and doom scenario seems to have changed in recent years, mutants still aren't anywhere near the population they were at the height of Morrison's run.
If you count moments in which the Earth's reality has been temporarily changed by entities like the Scarlet Witch, it's quite possible that the ACTUAL point at which there were more mutants on Earth than ever was during House of M, because in the modified reality the Genosha attack hadn't happened and mutants were dominant enough that they weren't being randomly exterminated. Or perhaps there was some obscure plot where every human became a mutant for a few seconds. Or, the universe being full of powerful beings and time travel adventures and all sorts of other shenanigans, there might plausibly have been, off-panel and unchronicled, some other reality shift that happened briefly and left the world with a much higher mutant population, but was reversed with nobody is aware of it, until some writer decides to retcon it in.
But in history as most people know it, it looks like Morrison's run was the height, and somewhere in the neighborhood of 30 million.