The biggest challenges, technically, are 3D graphics and Networking. Network interoperability between Linux and Windows will rarely happen, because companies often use the proprietary Directplay library which cannot be ported over to Linux. We have created a multiplatform alternative, called Grapple, and we hope that over time, some Windows developers may pick this up to use in their titles, allowing cross platform multiplayer.
Quoted in Robin Heggelund Hansen, "Porting games to Linux" hardware.no (2009-03-10)