So far I can't argue with any of the advice given, so let me supplement the plot and RP advice thus:
Plot:
1) Interview (just a formal word, doesn't need to be formal) each player finding out their character's motivations for becoming an adventurer. Why do you do what you do? Have them come up with a small back story and then exploit it. That doesn't mean kill and kidnap families - that's so over done it's tired, but there are usually one or two things you can run with, even as side adventures.
2) Keep a log at your table. Write down things the players/characters say that might trigger ideas. If Bob playing a halfling rogue keeps wanting to interact with other halfings, which you haven't provided thus far, design a halfling encounter. Someone has a hatred for orcs of a certain tribe for what they did to his/her family, give clues to where this tribe is located and set up a revenge encounter. Whatever, keep your ears open to the little off-handed comments, they pay HUGE divideneds.
3) Never be so proud as to not admit when you've made an error in scripting, judgment, whatever. Not really a design help, but I have seen more than one really good group get run off the rails by a single bad night where the DM was too prideful to say..."ooops, I screwed up, can we back this up or can we forget this ever happened?"
RPing
Generally, I would say, make every NPC memorable. This doesn't mean stat every NPC - you'll go insane and your workload increases by the thousands for a small town. Outline a few major re-occurring NPCs if the party has a permanent base, and even as they pass through locations, give your NPCs names (a quick list available from just about anywhere is helpful), descriptions and quirks. And of course, make a note of it, because invariably they will want to talk to Judy the bar wench in Haverbrook again and if you don't keeps notes when you say "Who?" you'll get lynched - trust me on this.
Another habit
to get out of is saying things like "the bar maid says....", or "the guard says....", try to speak to your players in character. No you don't have to take acting classes, and you really don't have to be all that good, but the effort will make the difference. You'll notice they will follow suit eventually and stop saying I tell the NPC .... and will start to develop personae for their characters.
It really is in the little things that you do that will make the difference. I always laugh when I hear people say that "fluff" doesn't matter. I beg to differ, it makes much more of a difference than the "crunch" when making your game memorable. Most people never remember "beating BBEG #3 way back when we were 5th level." But the tale of defeating Talifer the Black in the epic battle of Fort Ravenwood will ring on for years after the campaign ends. Ask people that have played in P-Cat's M&M games at conventions or Crothian's Paranoia con games. I have had the pleasure of seeing the first and participating twice in the second. All of these were one off's but had so much flavor that they were more intense than many on-going campaigns I've seen.
Hope this helps! T-Foot.