There is a number of big issues, but not all of them is known.

If your looking at the Kernel only... The list would be...
  1. The absolute biggest would be that there is No stable Driver API between kernels. The Driver API constantly breaks between releases, and this drives away Device makers that wish to support linux. Most device makers want to write a driver once, and then expect it to work for the major version. A Good example of this would be to write a driver for linux kernel 2.6.x where the driver binary would work up until at least version 3.0.0. However, as it stands now the drivers constantly have some form of api breakage between kernel releases.
  2. ACPI/Power Management issues taking battery life from consumer laptops.
  3. Microsoft, and the UEFI Secure Boot. Vendors are likely to support only Microsoft and lock out anything else.

If your looking at Graphics drivers:
  1. Constant fighting between graphics drivers. It's impossible to have a system configured to have a mix of graphics cards without serious technical knowledge. Mixing and matching the Following graphics cards are guaranteed to have major problems arise.
    • Radeon Series ( Open Source Driver, Current )
    • Radeon series ( FGLRX/Closed Source driver, Current)
    • nvidia (Open source, nouveau )
    • Nvidia (Closed Source, Any model)
    • Intel Graphics
  2. Switching between graphics cards without modifying Sessions with ease. For example, I would want to be able to Switch from the integrated graphics card to the dedicated graphics card when I play games, but when I am done, Switch back to the integrated to save power.
  3. Incomplete device Support. No support for OpenGL 4.x in open source drivers.

If your talking about Software and Open Source in general, the issue is below...
  1. Software Patents that prevent implementation of Specifications. For example Mesa had a lot of issues with the patents over the S3TC patents
  2. lack of commercial video games ( Like Unreal Tournament 3, Halo, etc ) being Released natively on linux. Iinstead these games are increasingly being released on Mac OSX using libraries that are cross platform. Generally Speaking, This is a major issue because a lot of these games use libSDL, OpenAL, OpenGL, and a few other libraries that are also on linux.
  3. Digital Rights Management demands by major content creators/providers. This on It's own is inherently incompatable with GPL, but is manditory if you want anything to do with consumer media ( Video Games, eBooks, Blurays, DVDs, etc). This is also why there is no decent HDMI capture cards that work on linux that users would want to use. For this, A good example would be wanting to capture a high definition stream of a video game you are playing on a Playstation 3, Xbox 360 or other major console.
  4. Even though this is not Linux Specific, it is key... The GPL Compliance is abismal, and companies within china are usually the main instigator. This issue will only increase, and any action to corect this will only hinder linux overall because it'll scare companies away. While I mention china, there are also amarican companies that develop and release successful products that use Linux ( for example, Android tablets and routers) and then fail to comply with the basic license agreements involved. In any case, If you compare Linux and most other Open source products to the closed source alternative you wind up with a reliable comparison of the Open source product being a Reliant Robin, and then the Closed source product could be a Lamborghini Diablo.