I read in two sources that the 2016 popular vote was Democratic by 2.09 percentage points (48.18% Clinton, 46.09% Trump). I also read it was by 2.22 percentage points (51.11% Clinton, 48.89% Trump). I assume the second one is the two-party vote. Is that correct?
Yes - the official totals according to the FEC were:
Trump - 62,984,828 (46.09% of all 136,669,276 votes) Clinton - 65,853,514 (48.18% of all 136,669,276 votes)
So in terms of difference in popular vote percentage, this gives us your first figure, 2.09 points. However, in terms of the percentage of the votes given to either of the two main parties, this gives us:
Trump - 62,984,828 out of 128,838,342 = 48.89% Clinton - 65,853,514 out of 128,838,342 = 51.11%
Calculating the difference between these percentages gives us your second figure of 2.22 points.
Donald Trump Hillary Clinton Popular vote 62,984,828 65,853,514 Percentage 46.1% 48.2%
Which gives Clinton a 2.1% advantage.