‘Strategies’ for creating own layout/styles?

Hello,

new to WordPress, but familiar with CSS, I’m having a hard time figuring out how to go about modifying the overall layout and design. It takes me forever to ‘reverse-engineer’ and figure out somebody elses work and ‘logic’ behind things.. >.<

What would be a good ‘strategy’ for this? Create something from scratch? Modify some existing theme? How do I then know what styles I need to match generated content?

Ideas or suggestions would be very welcome ??