The no-longer-produced high-end Walker (what was that, like $350?) was definitely the best looking spyderco I've ever seen. It had Walker's typical well-done and balanced design style, married to good-looking materials. Beyond that, the knife I really like is the Viele. Viele has developed a nice little style, and it translated wonderfully into the Spyderco collaboration. Viele has a more recent collaboration, I think with CRKT, that I feel doesn't succeed anywhere near as well, aesthetically.
For me, the in-house designs are incredibly well-designed knives from a performance perspective, and in fact my favorite knives from Spyderco are all in-house designs. But aesthetically, they lack the lines and flow of many of the collaborations. Best looking in-house would be the Calypso for me, which actually does approach the sleeker custom styles.