>>227469
First, you've got to be into it. You should be either the most, or at least one of the most, enthusiastic participants at the table. You absolutely cannot afford to be too cool for school. Roleplay hard, and don't be afraid of looking like an idiot; you're going to have to set an example for them, especially because they've never played. Personally, I'd make sure to have at least a couple funny voices to do. A high-pitched goblin/imp kind of thing is easy and fun, as is a gravelly old wizard or dwarf type. If you can do accents well, that's always a winner. It's not for everybody, and the fact is I suck at impressions and accents, but it establishes that I'm willing to go out on a limb to have a good time. Other people will follow suit when you break the ice and it's clear that they're not going to be judged for acting a little goofy.
Second, you've got to know the rules. Whatever ruleset you use, understand how it works and be at least fairly comfortable with it. If it's a new system you've never done, play around with it a little solo. Run a battle or two and see how it goes (if it's a game with a lot of combat rules). You certainly don't have to be a slave to the rules, or memorize every detail of them, but you do have to know them and be able to apply them reasonably quickly.
Third, have some kind of plan for the session. Maps, encounters, cool situations, plots, NPCs, etc. If you've never run a game before, a pre-written professionally published adventure is not a bad idea, but not essential. If it's a crunchy game with a lot of numbers, prepare at least some monsters and NPCs with the numbers they'll need beforehand rather than pulling them out of your ass on the fly. That said, don't be a slave to your prep work, even (especially) if it's a pre-written adventure. Try to gently shepherd the players toward stuff you've got prepared, but don't force them, and absolutely do not put the kaibosh on any clever/zany/unexpected solutions they come up with just because you didn't foresee them. Maybe they'll try to convert and reform the bandit gang rather than slay them. Maybe they'll blackmail the corrupt judge rather than bring him to justice. That stuff is cool, and it's what makes rpgs great. Roll with it.
Premade characters are not my favorite thing - I want to play the kind of guy I feel like, not what I happened to get. I'd have the players make their own, but premades are fine as long as everybody like their character. Don't force someone to play a character they're not interested in; either have more possible characters prepared than players, so nobody gets stuck with the stale last pick, or help them make their own char if they're not psyched.
One tool I use a lot these days is a name generator, or a big list of randomly-generated genre-appropriate names. When the players take an unexpected interest in some NPC, and he needs to upgraded from nameless extra to supporting actor, I find the name is the hardest thing to come up with on the fly.