It seems like the major difference between plotnine and lets-plot is that plotnine wraps Matplotlib (and thus works everywhere Matplotlib is available, but doesn't offer much interactivity), while lets-plot is written in Kotlin and seems to provide interactive plots.

The selling point is the grammar of graphics. See Wilkinson on the subject.

There is this new and very promising package that adds interactivity to plotnine graphs https://y-sunflower.github.io/ninejs/.

Disclaimer: I am the author of plotnine.