One important aspect of your game is the tone. Is it a light hearted comedy? Four colored comic book action? Batman style gritty realism? Generating a tone and adhering to it are both very important, and equally important is conveying to potential players up front what that tone will be.
Personally, I think the worst tone possible is a depressing, post-apocalyptic setting, or one in which the players are up against unwinnable odds, or playing in some other environment that is horrifically depressing. The best example of this that I can think of are the White Wolf games Vampire, Werewolf, Mage, etc. In them you play characters who are either in terrible situations (i.e. undead) or are fighting against opponents that cannot be beaten. In Mage, for example, your primary opponent is The Technocracy. The Technocracy rules the world behind the scenes, there is no beating them. Nothing you can do in the long run can overwhelm The Technocracy because they employ a kind of magic called Science that is powered upon a fundamental belief that science works. The more people who believe in Science, the more powerful it is. So guess what, mage; you live in a world that cannot possibly be changed in any meaningful way.
If you play Werewolf do you think you are going to be able to defeat The Wyrm? Think again. Vampire? Well, Vampire has a sort of cult following all its own. At least it did when I was in college when LARPers took it over and got to dress up in black and role play the undead making and breaking political alliances. Vampire might be the one exception in the White Wolf series because instead of their being an obvious major villain, the players themselves were villains (you know, for being undead blood suckers).
The point is, though, that when players are confronted with a world where they are pitted against an unbeatable foe, it can be pretty daunting. It is like my dislike of X-Men games. With X-Men games the opponent is the Federal government, mutant hunting agencies, racist groups, mutant terrorists, etc. There is no winning here. Your character is trapped in a nightmare world and the best they can hope for is to have a mattress to sleep on underground somewhere, hiding from hoards of racists bastards out to kill them because they are prettier than they are (ninety nine out of a hundred mutants are beautiful. It is the rare player willing to run the sort of freak of nature that would cause riots).
Your game does not always have to maintain the same tone. Perhaps you want to run a series of adventures with a humorous bent, or you wish to introduce more romantic elements. The tone is in part inspired by the players themselves as you strive to keep them entertained. For example, a player may wish his character to form a romantic bond with an NPC, if so then role play that out with them. Even if your game is not romance based it certainly does not hurt to have a romantic element to it, provided it is done in a tasteful manner and adheres to the rating system you and your players are comfortable with (I have always gone for a PG-13 rating in my games, although when it comes to gory elements I have slipped into "R" territory. But when it comes to sex, fading to black works best for both myself and my players). Sometimes a game needs to be shaken up a bit to keep it fresh, keep players interested. Do not be afraid to change up the tone a bit if you or your players are getting bored. Just bear in mind that if your players signed up for one sort of game and you start delivering another they may quit on you. Discuss dramatic changes with your players before you initiate them.
What about humor, you may ask? Funny is hard, and I cannot imagine any game that can be long sustained on it. All the same, I think a little humor never hurts. Some of Star Trek's greatest moments were funny ones (The Trouble With Tribbles, Trials and Tribbleations are just two examples). Just don't be surprised if your jokes fall flat, and do not take it personally if your players do not find them funny.
So when you design your game, think long and hard about the world you are creating. Do you really want to deliver an environment in which your PCs can have no impact whatsoever? A world where they are against unstoppable forces? A place where they are at best government stooges, at worst outlaw vigilantes with a price on their heads? Consider carefully what you deliver. My game has lasted over eight years in part because the tone I have provided is at times gritty, other times humorous. A place where sometimes the heroes do come across larger than life and make a difference in the world.