Organic town designs tend to lead to shorter paths to certain items.
Consider in the real world. First property in general, there is a bulls-eye shape of property value. As long as the city is growing and not blighted, the property value generally will go up city-wide. The city center grows to astronomical value after many years, look at places like London or Tokyo or New York City to see just how valuable that central land can be.
Terrain and natural features also affect the value. Beachfront luxury resorts with sandy beaches have one kind of high value. The heavy industry docks have another kind of value. But a rocky beachfront that is neither tourist friendly nor commercially friendly will often be blighted low-value dumping grounds. Cliff-side vistas, river-front or lake-front properties, hilltops, each have value.
When people travel the main roads, in the physical world there are critical items first. The first gas station will sell fuel to the people running low. The first motel will sell rooms to drowsy travelers. They can sell at a premium price while offering sub-par service because the travelers need the services urgently.
Inside town there tends to be clusters and districts. Entertainment districts, government districts, commercial districts, industrial districts, residential districts. As cities grow there are multiple clusters with various benefits and services. The cheaper industrial districts and cheaper commercial districts have bulk items of expected quality. The expensive districts have boutiques and specialty stores that cater to the rich, and their appearance and clients reflect it.
Since we're mostly talking about shops, those tend to be in easily accessible patterns. They're right along main roads because merchants need to move goods. There are the budget critical services when you enter town on the main roads, then a gap, then some mid-value services, then government services, and finally high value goods and services.
The low-value areas tend to be off in blighted areas or low property values. The hive of scum and villainy probably won't be next door to the police station, although you could place it next to some government buildings as a joke.
You won't find the areas to explore with niches and hidey-holes inside the expensive city center, there are too many people and the land is too valuable; anything that was lying around would be picked up immediately, unless perhaps in your story it was dropped from a wealthy store patron or something. Instead the explorable areas are on the fringes of town, out away near the forests or farm land where few people pass by and where it takes effort to pass through.
Those physical world aspects tend to be mirrored in games.
When you enter the main road you see a cleric to remove poisons or infections or an inn to help those with 1 HP remaining. You may pay a premium for them, and later in the game you can probably avoid those services completely, but early on sometimes you'll be limping in to town with a purple cloud willing to pay anything before those last few HP drain away.
Continue down the main roads and you see a place do dump the junk you've collected in your travels, the low-value shops. Continue down the road to find higher value shops. Then you get to either government buildings, or you get to high-value specialty shops. You journey off the main road to find where people live, or the places with good deals on everyday items, or to find the areas for exploring and looting.
The low value hive of scum and villainy for your rogue will not be on the main street next to the high-value shops, nor out among the residential districts, but out by the blighted areas. It may be by the polluted rocky seaside where bodies are easily dumped and small boats can be hidden for a quick getaway through the muck, or through a city's back alleys and dirty sidestreets. If you're looking for a rogue's poisons, this is the place.
