Build it with a text editor, old school
The single most important thing is to follow the best practices outlined in the WordPress Codex
Lots of code monkeys ignore that little bit of advice and end up making themes and plugins that break when you update the WP Core.
I'm tweaking a new theme I built based on the Twitter Bootstrap. It's fully responsive, looks great on my big panels and on my iPad and iPhone too
You might want to begin there for a quick jumpstart
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