What is the big deal about the grid layout anyway? If you aren't trying to design a site that has ultra-dense-content on every page like nytimes.com, what's the point? I mean, does everyone have to jock Khoi Vinh so hard? For most sites that aren't so heavy in content, floating content smartly and giving text ample breathing room is usually a sufficient starting point.
The grid system reminds me of Ansel Adams' zone system for photography... it's good for teaching students about the elements of visual balance, but ultimately it's a pedagogical scaffold. IMO when the grid system and the zone system become a heavily used crutch for your design and art, that's when what is created tends toward stodgy and boring.
In the context of web-based startups, you can assume 99% of the time content will dictate the design, and that the site will grow in content rather quickly. That said, the grid is one of the most modular structures for plugging in content without disrupting or rebuilding the entire flow.
Why re-invent the wheel? The grid concept is universal, and certainly helps during planning for prioritizing real estate and architecting your information properly.
The reason I use YUI is that I suck at CSS, and, rather than spending a disproportionate amount of time figuring out floats and breaks and browser incompatibilities and whatnot, I can get going quickly.
The grid system reminds me of Ansel Adams' zone system for photography... it's good for teaching students about the elements of visual balance, but ultimately it's a pedagogical scaffold. IMO when the grid system and the zone system become a heavily used crutch for your design and art, that's when what is created tends toward stodgy and boring.