Contrary to the name the proof of work used in Litecoin is significantly more difficult than SHA256 to verify (it slows sync times noticeably), while simultaneously not achieving it's goals of being only able to be mined on a CPU, or a GPU depending when you read the pitch on their website. It offers very little resistance to being mined on a GPU or ASIC, in fact its design is extremely well tailored to linear time-memory tradeoffs, which make the hardware cost even cheaper. Being harder to make an ASIC for isn't an asset either, it just means that they become less commodity hardware and more likely a monopoly of one or two players.
SHA256 is about as lightweight and as simple as you can get, avoiding hardware acceleration is not an achievable goal and probably not even desirable even if it were.
2It's never impossible to build an ASIC for any given POW. After all, an ASIC is just a computer which happens to be application-specific. If it's "impractical to build ASICs" for a given POW, then only the super-rich will be able to build/purchase and subsequently operate such ASICs. If your goal is to minimize centralization in the long term (assuming that ASICs will eventually appear for any popular POW), then using simple algorithms which can be easily/cheaply implemented in ASICs should be your target. – Christopher Gurnee – 2015-04-28T13:31:59.880
@ChristopherGurnee: That should probably rather be an answer. – Murch – 2015-07-28T12:12:18.447