In my (relativley small) experience, HARP was the only ICE game that players of 3rd and 4th edition of "you know what" were willing to try...
Players and GMs of any RM version have all the books they need to play for some decades. HARP is more friendly to convert or bring in new gamers, and there is still plenty of room for new books.
Throw in a streamlined v2 with more options (combat à la carte, more or less skills, different casting spells options, etc.) and a major adventure path à la Paizo, and you could sell some, in my opinion... Many gamers today don't have time to write their own adventures, so you need to provide adventures with your system. As you can also double or tri-stat with free PDFs, you could have a wide audience for this (HARP, RM, d20).
For a HARP v2, I would think of a very simple core, with a lot of options in an "Options Book", Ã la Unearthed Arcana. New RPG rules should have a very simple core, people don't have time to digest 400 pages behemoth rules anymore. And then add every two or three months an expansion booklet (64 pages, cheap, color) with new professions, races, spells, talents, monsters, etc. Interesting to mix, as GMs AND players would like to buy it. Mixed with adventures, it should make the internet talk and generate a lot of interest.
For the setting, I would go with Shadow World, it's so hard to bring in an interesting non licenced setting these days...