I use D&D for fantasy. Full stop. If I am running fantasy, it is D&D.
If I am running a setting set in the 1800s, 1900s, or 2000s, I run GURPs. I feel the system gives me a better feel, even when there is magic involved. It just interacts better with 'realistic technologies'. I've also had some success running a homebrew system for a Cthulhu/Western game that was based upon a 4E system, but each character (pregens) had mechanics that the player had to figure out as they played.
For Future tech (Gamma World, Traveler), I use a D&D based system. Once technology gets that advanced, it is more like fantasy than a modern setting.
For a Superhero system, I run Champions (an older edition - might be first). I rarely do it, and Champions worked well enough. Learning a new system is too much work for something I run so rarely. I think any system used for Superheroes is going to be difficult. The power levels can get way out of hand, and the ways that powers can be used are too difficult to model in a game system effectively. I usually do pregens for Superhero games as it allows me to craft the rules around the Superpowers a bit more carefully before we play.