You want to get rid of murderhobos?
Give your PCs enduring connections to the community -- family, friends, professional acquaintances, organizations, and so on -- and then don't destroy them for cheap drama.
@benlehman I think it's important to note that even if you give PCs relationships, if you're playing a game whose rules mostly deal with how to murderhobo, and whose character options/level-up cookies are mostly ways to murderhobo, and the means of advancement is via muderhoboing; then guess what? You're still encouraging muderhobos, you're just whitelisting some key NPCs.
You want to get rid of murderhobos? Play a game that's not about muderhobos.
Liiiike... the one I'm making. ;)