Hi GG,
I have downloaded and purchased epubs up to 75mb. They are slow to load initially, but then they seem to work fine (on a variety of Nooks and a Nexus 7 running Moon+).
My preference would be one epub, containing the larger images, since my experience has shown little drawback.
22mb is about the same size as 4 or 5 mp3 songs, so for readers the value per mb is there.
If my division is correct, that's still less than 100kb per image, so they are, on average, quite small. How does the book look on a 1920x1200 display? Perhaps they need to be larger
Few books will have 300 illustrations, so the impact on total storage requirements isn't an issue.