This question could be taken two ways —  mechanics end of things (I run X system because I get it), and what kind of setting you run well. Let’s start with the second:

Back in the midst of time, when MTV was still doing music and everyone was worried that Ronald Reagan was going to get us all killed, I started playing RPGs in earnest. I’d found a few folks to play with at school — and this was back when furtively letting people know you played D&D was like being a drug user (“Hey, man…you play..?) and the wrong person might lead to embarrassment or a beat down — and i was trying everything out there: Dungeons & Dragons (no “edition”), GangbustersTop SecretGamma World, or the non-TSR stuff like Traveler, and later James Bond: 007, Universe, or Twilight: 2000.

One thing I found quickly was I didn’t like the way the TSR games handled injury — hit points as a combination of physical damage, mental stress, or luck just didn’t feel right. You got “hit” with a sword…you don’t just walk that off. (I still hate that aspect of 5th ed.) I also was a huge Bond and action movie fan. Top Secret and James Bond rapidly became out go-to game in 1983. I researched the hell out of intelligence agencies, terrorist groups, spycraft, guns, cars, whatever I needed to give the game a realistic feeling, while still playing with the action movie tropes. The other big game was Traveler, where the setting was really left up to you. In all these cases, story was the thing, and I wanted rules that worked with me to tell a story, instead of being there to be rules lawyered. This is why GURPS and Hero were to me like silver to a Hollywood monster.

Along the way, that meant that game systems that pushed character creation and storytelling over hack-and-slash became my preferred genres. Dungeons & Dragons and other fantasy games were consigned to memory until very recently. I had a period of running superheroes and prefered DC Heroes to the more abstract Marvel because you build the characters with strengths and weaknesses. Weakness was something a lot of players eschewed in the ’80s, save to get a few more points in their creation. Weaknesses, flaws, problems — these make the characters interesting. Interesting characters make the story interesting.

I might have taken to the White Wolf material, save for the overwrought vampire thing and the attendant LARPing, which a few times playing seemed to me an excuse for people to flirt and hook up. My interest in verisimilitude that started with James Bond, meanwhile, had driven me to embrace the Space:1889 setting — sci-fi, history, cool gadgetry…it led me to study history.

Now, the easiest games for me to run are ones where the setting really entices me. Victorian science fiction, ’30s pulp action, most recently Roman gritty fantasy, and established universes that have loads of material to work with. Central to most of these games is some aspect of intelligence work, bureaucracy and politics. There’s something to be investigated or solved, questions to be answered — sometimes as simple as “where is the missing girl” to “how does morality work in a universe with multiple gods who value different “good?” I need a setting that makes the players and characters engaged with the questions asked.

When it comes the to systems that I run best, they usually have to be simple enough to quickly grasp and not lead to ambiguity in play. They need character’s flaws to actively affect them in some way. Combat had to be crunchy enough to feel real, but slick enough to run cinematically. For that reason, I usually like some kind of hero/fate/plot point mechanic that can be exploited as a “get out of death” card.

The one that works best for my style of GMing is old Cortex. Simple, with loads of support for building good characters. The combat’s got a few quirks, but it’s not awful. Next, I like the old James Bond game. Partly because I know it so well, partly because the mechanics — especially for combat and chase scenes — really captures the flavor of action movies. Fate is also pretty easy to run. The character creation allows a lot of latitude for playing up your flaws and strengths (sometimes at the same time), but the consequences approach to damage, while it covers other kinds of “damage” than physical, feels like it lowers the stakes. (I know, the idea is that there are worse fates that death…) Ubiquity, while I like the basic mechanic, has some really issues with its math and combat is a hot, old school mess that works because I ignore almost all of the special maneuvers, etc.

That’s a really long winded way of saying I’m run rich settings with rule light systems.