Even if you aren't interested in science... this game will suck you into looking at all sorts of bleeding edge stuff. You might not think programming rat brains is a fascinating field of research now.... give it 6-months on this forum and you will.

I think there has been several advice threads in previous threads, maybe somebody could tie together a bouquet of links to them? My main advice is to start out gently, yet right in the middle of transhuman weirdness. Show the players just how strange the world has become, yet do it in a fairly "safe" environment where they can gradually be introduced to the really wild aspects like resleeving, forking and rep economics. I think I described it earlier, but I did one intro adventure that started with the PCs getting restored from pre-Fall backups. They got a rough description of the world from a benefactor, set out - and got immediately killed... only to wake up resleeved at a hospital, with a bored policeman trying to figure out the cause of the "vandalism". Then they got a chance to select enhancements, go out into a town, and gradually get involved in the bigger world. Current state (it is a bit on hold) involves space travel and meeting some of the more radical factions.

Here are some recommendations I would give to starting GMs. [list=1][*]Don't sweat the rules too much right now. The first few sessions are a learning experience for the whole table. Don't spend too much time flipping through the books; make a quick judgment call and keep the game moving. If it's too tough to judge easily, pick the decision that favors the players. Keep it fast and fun… you can get deeper into the rules once everyones comfortable with the game as a whole. [*]Recommend that your players get extra Moxie for their characters. Moxie makes up for bad rolls and character decisions very well. Also recommend the Common Sense trait; it's a great excuse for you to give your players recommendations… like when they should be running instead of fighting. [*]Don't try too hard at introducing the whole setting to your players at once. Break it up and introduce your players to the whole thing piece by piece (one session let them try out egocasting and using different morphs, the next session let them fight some exsurgents, for example). As a general rule, if you are introducing more concepts in a single game than the quickstart does, you're doing too much. Arguably, if you're introducing as many concepts in a single game as the quickstart does, you might still be doing too much. Also, you might want to try out the quickstart. :D[/list]

Just to second what others have said: TPK's are a story beat, not an ending. I find the biggest challenge is not the mechanics (though hacking always does my head in), but rather the setting - there are so many possible courses of action available to players it can be difficult to successfully cope with the curve balls they inevitably throw your way, yet it can also lead to choice paralysis for players. That being said, the setting is the greatest asset EP has.

Another thought: try and come up with a way of streamlining gear and morph acquisition when far casting somewhere, through either plot (only splicers are available on this Jovian hab) or with a system. My players have three character sheets: their preferred morph; their second choice morph; and a splicer (which they are always guarunteed of getting). Their gear lists are split into sections: this is what you can get anywhere; this is only available on anarchist habs/through criminal networks etc. With the TPK thing, I've found I can't GM DnD games (EP is the first RPG I played and GM'd). In DnD you have to design combat encounters so they are challenging but not lethal, I process I find time consuming and stressful. In EP I just design what I think would be a fun encounter, and if they die, they die.