The current default theme for Hotaru is loosely based on the YUI CSS Grids from Yahoo! But YUI is just one of many frameworks out there that people use. I know 960 is popular, and I've started playing with Blueprint.
For Hotaru themes, it's easy to apply such frameworks to the skeleton of your theme, i.e. the index.php template, but because plugin templates are inherited, you can't apply your chosen framework's class names to the HTML in those templates unless you move them into your theme folder and edit them there. That could dramatically increase the number of templates in your theme.
So which frameworks do you like, and what are your thoughts on applying them to Hotaru?