(Jeff)> If you want to try an in-between thing, try laying out your pages as if they were two half-pages, top and bottom. While this will diminish your splash pages, it will make it so you can break your 24-page print comic into a 48-screen web comic, and the aspect ratio is exactly correct -- 6:4.5 = 4:3, just like your monitor. The half-page can be zoomed to "Fit to Screen" with the Acrobat window maximized, and it should be clearly readable. While some may see this as a restriction on their artistic layout, I'm going to try to look at it as a challenge. Of course a few full-page splashes aren't going to hurt...
It's the format I'm now using. I find it to be as restrictive as the comic page format is when compared to 11"x17". In other words: not at all. We're just not used to it yet. I can also create in full color without having to worry about prohibitive printing costs.