What would you recommend for a high traffic ajax intensive website?
Going to need more data.  Jeff had a few articles on the same problems and the answer was to wait till you hit a performance issue.
to start with - who is hosting and what do they have available ?  what's your in house talent skill sets ?  Are you going to be hiring an outside firm ? what do they recommend ?  brand new project w/ a team willing to learn a new framework ?
2nd thing is to do some mockups - how is the interface going to work.  what data does it need to load and persist ? the idea is to keep your traffic between the web and db side down. e.g. no chatty pages with lots of queries. etc.
Once you have a better idea of the data requirements and flow - then work on the database design.  there are plenty of rules to follow but one of the better ones is to follow normalization rules (yea i'm a db guy why ?)
Now you have a couple of pages build - run your tests. are you having a problem ? Yes, now look at what is it. Page serving or db pulls ?  Measure then pick a course of action.
For a website like reddit with lots of up/down votes and lots of comments per topic what should I go with?
Lighttpd/Php or Lighttpd/CherryPy/Genshi/SQLAlchemy?
and for database what would scale better / be fastest MySQL ( 4.1 or 5 ? ) or PostgreSQL?