Tabletop roleplaying is one of my favorite pastimes, and it's no surprise to anyone that my four thousand plus hours of experience with it come in a variety of forms. I grew up on Saga Edition, learned the wonder of the Hero System in high school, and played in some five or six 5e campaigns in college, along with a number of Fate games and some roleplay-likes such as Fiasco. In all of that time, I've never found two systems that are even remotely the same: each is different and unique in what it supports, who it caters to, and how it's intended to be used. Many GMs run one system, but all of the most experienced ones I've talked to have a number of systems in mind, and can pick one at leisure for their upcoming games. As the basis for everything you'll be doing at the table, the choice of system is critical to making your tabletop game a success.
For starters, you should be aware of your group's composition. Do you have a lot of 5e gamers? Will they be out of their element if you run Pathfinder, or will they appreciate the added complexity? Are you trying to run the Hero System, with it's 750-some pages of core rulebook, with a group of first-time gamers? Have you neglected the interests of a power gamer by selecting a narritivist system like Fate or Dungeon World, or have you passed over your method actor's subtle cues by selecting a system in which she can't play her favorite archetype? Like all decisions, choosing a system depends on who's at the table, and what other tables they've sat at.
Perhaps the most important distinction in this regard is player comfort. If players are uncomfortable with the rules of the system - especially if there are a lot of them - you have to be willing to take time out for explaining and clarifying things during combat, and that can be taxing on a group with little patience. For this reason, rules-heavy systems that the players don't know are bad for running one-shots and short campaigns. On the other hand, if you have a group of gamers bored with the systems they've been playing (like some of my friends who are in 3 or 4 D&D 5e campaigns at once), you might want to run a new system for a longer campaign. You might even want to try out a new system for three or four sessions, not committing past that until you see if you like it as a group. I know plenty of experienced roleplayers who love the Hero System for its complexity and depth - but they got there after years of experience with easier systems. That's where something like 5e excels - it picks up new players quickly and easily, and it caters to the widest possible audience.
The second consideration is whether your system supports what you're trying to do. It's possible to run a 5e space opera campaign, to be sure, but it's far from ideal. Gumshoe work, science fiction, and high-speed vehicular combat are things 5e was just never designed to support; you'll get nowhere without house rulings in abundance. In contrast, I wouldn't pick Shadowrun to run a standard fantasy campaign - it's great for its setting, but little else. Something like the Hero System or Fate is more general - and falling in at opposite ends of the "number of rules" spectrum, those two games should have you covered. For settings that are supported by a detailed set of rules, nothing beats specific, but for settings you've designed yourself, or for which there are no published supplements, you can't go wrong with a general system.
The third consideration is whether your system is narritivist or simulationist. These are the two main schools of roleplaying - one focused on telling stories, and the other focused on simulating combat. Games like Dungeon World are focused heavily on narration and on story telling - they emphasize role playing and character development above all else. Games like Fate are in the middle - the rules don't get in the way, but they're definitely there. Games like 5e are a step further in the simulationist direction - you get a lot of rules, and plenty of what Robin would call "crunchy bits," but you also get plenty of room for interpretation and flexibility in what your character does; skill rolls, for instance, can be applied in quite a variety of situations. At the far end of simulationist are things like the Hero System and Shadowrun - games designed to tell you exactly what happens, and how, when you perform an action. There are no surprises, no "open to interpretation" rules, just plenty of simulation for when you really want to challenge yourself tactically. There's still room for role playing, of course - these are role playing games, after all - but when combat starts or skills get dicey, rest assured there will be an entire section on the mechanics of leaping as they pertain to gravity and surface friction.
What your group enjoys varies, and what your campaign supports should vary too. I never rule out a system or pick one outright before I know my group; I always keep in mind their interests, playstyles, and level of comfort with handling obscure corner cases and mathematics. I don't run Hero with newbies, and I don't run Fate with players who want fine-grained combat. I do ask my players what they like, and I read how they react when I first pitch the game. If something needs to change, I change it - after all, many systems are toolkittable. Just remember that once you start playing, it's hard to go back and change your mind - all you can do at that point is tweak and bend the rules, not throw them out entirely.
As always, the most important thing is to have fun - the system is just a means to an end.
Until next time,
Recon, over and out