Regarding the question by Wizardofwar41 about how to run a sandbox: I've been running a completely homebrewed urban sandbox adventure and here's how I do it:
Make a map of the general environment. You can draw it up by hand, use mapping software, or even one of those online random map generators. If you have time, make a whole world map and then a larger scale map of the region where the adventure will start. If you're short on time, just start with the regional map first.
Create some points of interest. You can either use online random generation tools like Chaotic Shiny or just do it the old-fasioned way by leveraging the unlimited power of your own imagination. Either way, it pays to start vague. Don't waste too much time fleshing it out with lots of fine detail. You'll have plenty of time to create all those little details as you prep for each play session. Think of sandboxes as blank slate worlds that resolve their own details as the players come to interact with them.
Define a starting point. Think about a point of interest on the map at which you'll be starting the game, and map that place out in detail. Draw it up in Photoshop or one of the dungeon mapping applications, use an online random map generator like Gozzy's, or even just Google Image Search some maps that other people made. It will make your life easier if you make this starting point the PC party's home base of operations, to which they keep returning for rest and reculeration at the end of each adventure. Maybe it's a roadside inn or a small town. At any rate, keep it small enough to be manageable because this is where you'll be devoting most of your initial time on detailing. The players will be seeing a lot of this place, so you'll want it to provide enough atmosphere to make it feel familiar.
Make NPCs. Consider your initial setting that you created for #3 and think about what kinds of people might live in and around that place. What kind of environment is it? What roles and occupations are necessary to maintain a place like this? Draw inspiration from real life, from literature, movies, TV, comics, anything that you find entertaining. Thinks about people you know who have interesting personalities. Maybe you have an uncle who tells corny jokes. A character like that might make a good shopkeep or bartender. If you're concerned about your characters too closely resembling other popular fictional characters, then maybe make them an amalgam of one or more characters. Online tools like OrcPub, RPG Tinker and NPC Generator can take a lot of the tedium out of generating multiple NPCs. A very important thing to consider is that every regular NPC must have a name. If you need help coming up with names for your characters, you might try Fantasy Name Generators and Behind The Name.
Round out your NPCs Now start thinking about some rough backstories for your NPCs. How did they get to where they are today? What do they enjoy doing? What other characters are important in their lives? How do those interests and relstionships affect their motivations? How might those motivations affect their interactions with other NPCs and the PCs? Some of the NPCs should have some kind of long-running conflict with others. What is the nature of those conflicts? Maybe some NPC is a single parent of a child with a behavioral problem, who's constanty causing trouble for others. Maybe one MPC owes a large sum of money to another, or suspects another of a crime. Maybe an NPC just went through a bad breakup or divorce which is affecting their social skills. Or, you can even make some of these conflicts a little weirder... Maybe some the NPC suspects another of being a witch or a sorcerer. Maybe a child NPC has a pet that exhibits unusual intelligence, and a rumor is going around that there's something not right about that animal. Some of these inter-NPC relationships might necessitate the creation of even more NPCs to flesh out the stories. Go back and repeat #4 if need be. For example, you've written into the backstory of Zarth the shopkeep, that he suspects his nephew Gil of pilfering liquor and stealing from the cash box. So fleshing out that narrative might require a few new NPCs, Zarth's nephew Gil, his sister Zara (Gil's mom) and maybe a couple of Zarth's delinquent drinking buddies with whom he parties away the stolen booze and money.
Create a some inciting incidents and related plot points Now think about the relatinships between your characters, and come up with a few "inciting incidents" related to those backstories. Revisiting the conflict between Zarth and Gil, we need some way to involve the PCs in that conflict. We can do this by setting up an inciting incident whereby that narrative is revealed. For example, the PCs see Gil fleeing the store. He runs up to the NPCs and begs them to help him hide. They can decide to either help him hide, or else turn him in to Zarth when he comes looking for them. That that sets the narrative into motion, implicating the PCs. You can then make up some follow-up plot points based on the PCs reaction to the original incident. Maybe if they turn Gil in to his uncle, he later comes for revenge with his delinquent buddies. If they help him escape, he offers them a drink and invites them to participate with him on some petty crime.
Create map assets for each narrative. So the full narrative involving Gil and Zarth and Zara might need to play out over a few locations. You'll probably need a map of Zarth's store along with the exterior areas including the alley where Gil runs to hide. Maybe it also involves a meeting with Zane at his apartment above the store, and perhaps a confrontation between Zane and Zara at Zara's house. These environments may or may not need to be mapped out in detail right from the start. Think about what assets you'll need if the PCs decide to follow each narrative, and either create them yourself or Google them off the Web. Don't forget to stock your environments with lots of miscellaneous items, treasure, and populate them with random NPCs if necessary.
Make rolling tables for the inciting incidents. Once you've come up with 15 or 20 inciting incidents, put your favorite 10 into a list, reserving the others as backup. Number the list from 1 to 10 so you can roll a d10 to determine them as random encounters. That's how you randomize the narrative encounters during game play as the PCs navigate though the sandbox environment. You'll want to make different rolling tables for different areas of the map, depending on time of day.
Make monster encounter tables for different areas of the map. Consider what kinds of monsters or animals are likely to inhabit various parts of your map, and write them down in lists. Make up seperate lists for morning, daytime, nighttime, and dusk, according to whether the creatures are diurnal, nocturnal, or crepuscular.
Set random encounter threhsolds for each location on your map. Set an array of percentile values for each discrete area on the map, depending on how likely you reckon an encounter to happen. You'll probably want several likelihood ratings for different kinds of encounters at different times of the day. For example, a town marketplace at noon would probably have a high likelihood of an NPC encounter, but at midnight the chances would be less. The woods might have a 20% chance for a NPC encounter and a 2% chance for a predatory monster encounter during the day, but nighttime would have only a 2% chance for an NPC encounter and a 40% chance of encountering a predatory monster. Use your judgment for these values, and then adjust them during game play.
Be prepared to improvise. Have all your NPC sheets, PC sheets, maps, rolling tables and other assets ready to go on game day. Step through each narrative to make sure you have everything you'll need.
Play your sandbox game! While running the game, as the PCs enter a new area or travel a significant distance over land, roll on the appropriate encounter table for geographic area and time of day, to see if they encounter an NPC or a creature. If they do, then roll on the NPC or creature encounter table accordingly. If it's an NPC, then bring out that NPC's character sheet and describe the encounter, then remove it from the NPC encounter table (it's bad form for the same PCs to have the same encounter with the same NPC more than once!) and replace that table entry with one of the backups.