RE: Sci-fi and modern settings in a DnD game?
I haven't personally, but it's been done, with D20 Modern.
Frankly, I would have gotten far away from D&D long before now – but that pretty much sums up exactly my position on gaming at this point, "as far from D&D as I can get."
But if I'm stuck using what I can only assume is a 3.5 version inheritance, and I know the characters are going to want to go across the multi-verse and I need to be able to cover it, let's consider the options.
You are going to have to decide how the world works from scratch, then try to keep those rulings consistent, then watch them traipse through and ignore most of what your going to do anyway, and it's a lot of dead weight.
Go pick up Wushu (which is absolutely free and worth every penny of it), spend the 2 to 5 minutes that it would take to translate every single one of your characters into Wushu mechanics, let the hyper-cinematic fast action fall where it may come and then watch them nearly beg you to run your basic D&D game using the Wushu mechanics.
That solution is really only interesting if you really want to run a superheroes game. As reasons to run a superheroes game goes, that one is perfectly reasonable. But less interesting.
If you're going to get start playing D&D anyway, you might as well use the right tool for the job: D20 Modern, which has rules and guidance for all that sort of thing.
Personally, I would take that group down the Wushu path without even a blank. That is always going to give better role-play than pretty much any of the competition.
I would second this. You can try bringing D20 Modern into your campaign, but it won't work as well as running a general system that was designed for more diverse settings. As a "low budget" option, you can also just re-skin D&D mechanics with minor modifications: a suit of Full Plate at AC 18 becomes Heavy Body Armor at AC 18, a flamethrower can be represented with the appropriate breath weapon, a sniper rifle can be implemented as something like a crossbow with +1 die to damage, +3 damage, something like that. Spells can be re-skinned too, or you may want to create homebrew ones with unique flavors for your various settings. If you want to go the "high budget" route, pick up a general-purpose system for this kind of campaign; doing so will require some investment from the players, but I trust the recommendations of lextenebris for finding a fun one to run. He knows his stuff.
I would loathe picking D20 Modern since the multiverse is vast and I kinda want the freedom to go from modern Tokyo with magical girls, to Warhammer 40k kind of setting. I still want the characters to use DnD skills and combat in those settings, since their power is tied to that part of the multiverse.
Anyway I will checkout Wushu.