It would appear that Sony Computer Entertainment America is expecting a second Infamous game. They recently acquired the domain name infamous2thegame.com and have tied it to their name servers at SCEA.com

Registrant:
SONY COMPUTER ENTERTAINMENT AMERICA INC.
   ATTN INFAMOUS2THEGAME.COM
   care of Network Solutions
   PO Box 459
   Drums, PA.  US  18222
   
   Domain Name: INFAMOUS2THEGAME.COM

Gamerankings.com also have the game listed with an expected date of 2011. Sucker Punch is also listed as the developer.

This comes as no surprise as one of the voice actors Tweeted about commencing work on it back in October 2009.