This is a bit of a brain dump - and is in no way a complete list - but it may be helpful to someone (especially the drupal theming bit).
My work flow is to first get the nuts and bolts of the site working - then play with the design - and finally add the content.
Assuming you have a basic install of drupal then here we go!

Decide on the content types (administer>content management>content type) and edit how these posts will work.
Edit post settings (administer>content management>post settings) for number of posts per page and length of trimmed versions.
Add a new vocabulary to the taxonomy (administer>content management>taxonomy) and add the tags you will be using - used for menu making later.
Set up some example pages/stories as the basic structure of your new site so there is something to work with - remember you can edit them later.
Enable clean URLS, assuming you want this - and why not? (administer>site configuration>clean urls)
Play around with URL aliases - so you don't have links that are /node/4 which is, of course Pants! (administer>site buildingt>URL aliases)
Get your menus built (administer>site building>menus) primary links etc. using your new aliases.
Now for fun, adding new modules. There is no easy answer to which modules you need as each site is different, but some of the ones that I have used are:
"service links" which adds digg, reddit links.
"bookmark us" the best cross browser script i've found to bookmark your site in a browsers fav's list.
"bad behavior" which prevents spambots from posting crappy links into your comments and forums.
"views" which allows you to change the new-old posting structure that is hard-coded into drupal.
Now it's time to enable all the modules you want and configure them to behave themselves (administer>site building>modules).
The next step is to put the module/block content in the right places in your website (administer>site building>blocks).
And that's the end of the nuts and bolts - now it's time for the dudes to get designing. You can choose a default theme, or download one of the others on the web, install it and configure it in (administer>site building>themes) but that won't get you an original looking site.
You can make your own theme - navigate on your web server to sites/all/themes/ and make a new folder with your new theme name. Then add an "info" file called new_theme_name.info - this is a text file with the following info in it...

name = new_theme_name
description = Description
core = 6.x
engine = phptemplate
regions[left] = Left sidebar
regions[right] = Right sidebar
regions[content] = Content
regions[header] = Header
regions[footer] = Footer

then make a new drupal theme template file called page.tpl.php - this is your html template with divs and php content script. Making this can be a bit of a challenge to begin with.
If you've never done this before then it's best to go to the current theme folder and copy the page.tpl.php that your site is using- you can use this as a guide to what php scripts are in which block and what they do.
Make a new css style sheet and make it look good - link this in the page.tpl.php file and save it in the same location. You might also want to use images in your css styles - so make an images folder in your new theme folder and place any images that you need in here.
It sounds quick - but getting your site just how you want it is down to your css skills.

Other things you might also consider doing is check that your mail server is working and that you have the correct permissions set. Try creating a new drupal account, do you get the confirmation email? Can the new user log in, post comments/stories or whatever you would like them access to? Can they be naughty and destroy your site? You may need to play around with roles/permissions/access rules in (administer>user management>..)

Then all you need is the content...

Have I missed anything out? Not sure, why not comment on what you do.. and what works best for you!