Shadowrun style campaign to me is defined by players taking advantage of conflicts between parties that have a lot of resources and power. Shadowrun on its own is not restricted to one city and you don't need to restrict to one city at all.
A campaign like this can be boiled down to the following elements:
- Characters working in the grey zone
- Contacts and streetwise will be important
- Betrayal, corruption (magic and social) and absence of trust
Characters working in the grey zone
Unless you make use of alignments, you should discard their importance right away. Reason being if a character is a cleric of a good or lawful good god, some activities related to this kind of campaign will conflict with character's alignment. Unless you take a good liberal look at it and say that a lawful good character can use motivations to explain why he would assassinate, steal, infiltrate and spy. Another bet would be to have all characters be closer to neutral than the two extremes (CE and LG).
Contacts and streetwise will be important
Having contacts is essential in a game like this. Shadowrun or not, if you play a game in which your PC are dealing with great enemies, they need contacts. I don't remember 4E covering mechanical aspects of contacts but I would use a liberal approach and simply ask the players who do they know. You can give them free contacts based on their Charisma modifier (min 1) and ask them to describe them in the limits of the setting.
A character playing a Warlord for instance may tell you he knows a guy working for the city watch and he owes him a favour for saving his life years ago. A rogue may have a romantic business with a member of the local thief guild. Any time they would use their contacts simply make a judgement call if they are available to help and how. NPC with big influence and power are usually busy.
Betrayal, corruption (magic and social) and absence of trust
Even if the whole setting happens in a candy world and everyone is happy, make sure the players see the world differently. The city described in any book can be seen from the other angle. It's not because pollution, rats and crimes are not described in full detail that they are absent. Far from it. Noir should be the major theme of your campaign. From my personal experience Eberron is perfect for that. Sharn is a great city for political tango and Shadowrun-esque game. The city is huge and there's multiple layers to exploit (both metaphorically and litterally as the city is built on levels).
Make the employer insist on being anonymous and the characters should watch their back because you never know when that Mr. Johnson could have them lock and tell everyone he captured criminals sent by another lord to steal from him.