TL;DR: How do you design a ruleset for a Civ-style TBS game that prevents city smallpox from being a profitable or viable strategy?

Long version: Civ-style games are pretty great. Bringing a civilization from cradle to grave is a great endeavor, and practicing diplomacy with hard-line human players is fun and challenging. In theory.

In practice, however, many of these games has, especially in multiplayer, exactly one viable strategy: City smallpox, a.k.a. infinite city spread, a.k.a. covering all available space with 1-citizen cities, packed as tight as they will go. I suppose this could count as emergent gameplay, but still; it could hardly be considered to be in the spirit of the class of game.

The Civilization series, of course, is stuck in their more or less fixed rule sets, established with Civilization. Yes, there have been major changes in some respects, but the rules pertaining to city building and maintenance have stayed pretty similar.

So the question, then: If you build a ruleset for a TBS from the ground up; what rules should be in place to prevent Infinite City Sprawl from being a viable strategy?

Or should ICS be a viable strategy?