Basically, it'd be another full virtual reality game, but with a couple of twists:
One, you only get a single chance to create your character (who will take at least some visual cues from how you look in real life)...
...And two, you only get "one life". If your HP falls to zero, your character dies, and because of rule one, you can't make another. You're gone from the game, for good. (There is some leeway here: both by magic and by some technology, it is possible to--for a brief window--revive a deceased character, but once that window is lost, they're gone. Some supernatural beings have revival mechanisms as well. But it should be noted: every method of revival has a failure chance, and the more times someone is revived, the higher this chance becomes. Revived characters also suffer from revival sickness, being slower and more sluggish for some time.)
Three, while the system technically deals damage off of stats, it still works off of mostly-real physics: you can't tank an arrow barrage unless you've got a magical/technological shield of some sort over you, because if the arrows connect, your internal organs will receive the appropriate damage, killing you instantly.
You can't fall from unlimited heights and survive, unless you have the abilities required for that to be nonlethal.
You can drown unless you take measures to prevent this.
You can't die of thirst or starvation, but you will physically weaken if you don't drink and eat, plus, you feel thirsty and hungry and start suffering from symptoms of dehydration/starvation if you ignore that, which over time can basically leave you wishing you were dead.
If you're a puny little 4' dwarf, and you try arm wrestling with an 8' monster, it doesn't matter what your strength stat is. It matters what your mass is, and unless the monster has a light mass/you have a heavy mass, the much larger monster will overpower you.
If you lose a limb, it's gone for good, unless you specifically have the ability to regenerate, or get someone who can regenerate it for you. (That said, it's also possible to buy replacement limbs, even though there's tons of ways both magically and scientifically a limb can be regrown.)
The game has a physics engine, but in select ways: bullets, arrows, and other projectiles can be shot straight, but they can also be shot and arc; this is a user-controlled function, meaning trick shots are far easier to pull off. However, gravity is a harsh mistress still, as indicated above.
The game in question, and what the comic would therefore be named, is exactly that:
Once in the game world, it is a fantasy setting, where there's magic a plenty, and similarly, a wide array of fantastical creatures that the player can be and/or encounter...but it's set in a "20-minutes-into-the-future"-day world, which (given the comic itself is in the future) is at sci-fi levels of tech.
Basically, mixing fantasy, with urban fantasy, with sci-fi, to create a realm where it's just as easy to get plastered by monster, by magic, and by technology. Bows, guns, fireballs, they all work in conjunction with one another. The game does have rules on what is and isn't allowed (for example, when it is and is not illegal to kill a player), and it's basically a really realistic hybrid of the real world with a fantasy world, in that it has full economies, full cities, full luxuries...everything that a player would want from a game, and everything someone would want from their life.
There would be NPCs, who have developed intelligence and have the appropriate level of respect. There would be monsters who are mindless beasts, as to give players something to fight. Bosses can be either, with NPC bosses being illegal to kill (not to mention, nearly impossible to kill--merely, brought down to a certain HP threshold where they recognize defeat), and monster bosses respawning after time.
There would be quests offered and given, by both NPCs and other players. Guilds, alliances, factions, even nations exist, some controlled by players, others by NPCs. The game would have a full world with three natural continents, a fourth continent on the ocean artificially constructed, and a fifth continent being constructed in orbit (so, four finished, and a fifth being built).
The game would have all sorts of stats and leaderboards and tracking and whatnot, but ultimately, nobody knows what the end goal in the game is. Common opinion seems to be there is none, that it's a sandbox world for fun and for connecting to others. Those that do believe there is some sort of objective to be completed have merely speculated. Some say it is intended to have one, but the objective has yet to be installed. (The game continuously updates, like many games do.)
Yet a small minority feel there is an objective, and it's already in the game, it's just a matter of finding it. And one such character would be our protagonist, a human magical girl, who uses a combination of magic and advanced technology in her fights. Her specific style of fighting involves dancing around and evading attacks, singing in order to buff herself/allies and debuff the enemy (not to mention, replenishing her mana), using her technology as an initial lead into the fight, and finishing off with magic.
This strategy can be adjusted as needed, such as attacking with magic and then using her advanced technology, not to mention, harvesting the power of sound to deal actual damage rather than simply weaken her opponent, but it's a fighting style that requires a lot of grace, speed, charisma, and intelligent use of simple tricks.
And by no coincidence, those traits are what make her a magnetic hero, as she draws together others onto her quest.
The game, One Life, can't be won by a simple fight.
No amount of boss battles, no amount of fetch quests, no amount of conquering, no amount of money, no amount of anything can win the game. The game can't be won by climbing to certain stats, or becoming a legend.
Her belief is that in order to win the game of One Life, one has to truly make it a life: to devote themselves entirely to it, with a purpose of making a difference in there. She feels that if this can be truly achieved, that the game would be won for that player, and her plan to go about doing this?
She plans on bringing about an understanding, one that would transcend the game and extend into the real world. She wants to unify people, bring them together, and to engage in only the battles which must be fought, and even then, only to protect. This is a belief others write off as hopelessly naive and idealistic, naturally. A folly born of youth and innocence.
...All the same, doesn't stop them from following her anyway. And over time, her goals slowly begin to succeed, as her influence extends beyond the game.
That's about as much as I plotted out, but I have a fair idea of the setting I want and what I want her to be, it'd just be a matter of plotting out the details of the story, and giving her a rich cast of characters showing off both the diversity of One Life, while also still allowing me to have it be a story largely on the magical girl focus. (This magical girl being all three types: lyrical, witch, and warrior.)