I would prefer Sheldon to be alone (I don't think he's suited for relatinships), but if he had to be in a relationship, I would definitely prefer him with Penny. Because I think they do have chemistry, but I also think that Penny knows how to deal with him and wouldn't put up with his crap. The Shamy dynamics are gross to me - she is so desperate to be with Sheldon that for the most part she just caves to his whims. She doesn't seem genuinely happy with him, but she clings on because she loves him and doesn't want to let go. Penny and Sheldon imo would be a more balanced relationship, though it probably wouldn't work out either.
That being said, I think I would find Sheldon kissing or playing a sexual version of D&D with anyone awkward.