I've definitely enjoyed a good mission-based RP in the past, so the idea can work; there's just the question of a motivating plot. Ultimately though, that's going to come down to you as the GM, otherwise it isn't your roleplay. That being said, here's a couple of ideas I can come up with.
Magic: The Gathering--Due to the sectioned nature of the Planes, and the uniqueness of Planeswalkers, I could see this making for a fun RP. The only issue you might run into continuing where the lore is at right now is finding a canon enemy. Or make one up. Or make it parallel. (Return to return to Zendikar?) Of course, this is just a nerd's musings, ignore this if you aren't a Magic fan.
A supernatural, almost Bleach-esque task force sent to deal with evil spirits. This is similar to that RP I mentioned at the beginning of my post, but that one had its own things going for it.
A fantasy setting; most likely an adventure guild. Get payed to go dungeon crawling, or slay a beasty, and so on. This one might work best with the semi-sandbox you seem to want, since there will be the Guild Hall, where one can spend their free time, then go off on missions. Possibly could even let players decide the missions they want to go on (with a minimum to keep up activity of course).
I'd be totally interested to see your ideas now that I've put in my two cents.
I'm definitely a Magic fan! But the lore is so expansive and I wouldn't want to wreck the cannon by any means. A parallel is an idea, but I feel like it might still restrict creation so I'd like to ideally do something completely original. It could be based off certain elements surrounding MTG, but I wouldn't want to draw too heavily on any real plot from it.
I'll just say, regardless of settings, I've had a fair amount of success with a mission-based set-up in the past. It's a good style of RP for people who have trouble coming up with their own overarching stories and makes it easier to promote/force interaction.
Yes, it is. My only question is if I do end up drafting this, would I be better off making like multiple small missions chooseable by players, or force them to all go on the same one? My issue with the first is that some people might feel left out, they might have a hard time finding other players to go on missions with them apart from the story designated ones. The other issue would be if it would cause the pacing of the story to go too slowly. I like it a little better though, because it lets players more directly choose to do things they are interested in doing. I could potentially make , like, a story mission have like two or three parts as seperate missions and all the players group together to do their part or could be assigned or something.
And just as I typed that, I wonder if it would be a good idea to assign players to "squads" ala the style of say... Naruto and then they can go on missions that way. At least that way, people would always have someone to interact with and they wouldn't need to worry. Hm.... ideas ideas ideas.
EDIT: I also don't want to publish an RP and have it not pick up due to the sheer fact that RP community around here seems to be waning at the moment. Can't have the same like five people playing in 6 different RPs... Well, I mean it probably could but it might wear people down.
Just some random musings.....