Hi, There can be a number of approaches u can think of. I am listing some of those based on my recent experinces :
1. Try to have minimum no of tpl files in your theme folder. We should avoide writing separate tpl for each type of content or node
2. Try to include internal css & js files on at the apprpriate location under speific hooks or so, sothat those don't get loaded unnecessarily
3. Try to make use of modules like cache_external_files to load external js files from ur local system and get it updated on cron run
4. Write ur code under best possible drupal way, I mean say, if we can have some code be working under page preprocess, we shouldn't write it in hook_init.
5. can take help of sites like http://gtmetrix.com/ , newrelic to check the site performance & follow the suggestions they provide
6. Combine images using CSS sprites
7. Leverage browser caching
8. Enable gzip compression
9. Use boost/mamcache, but be careful as boost has an issue with SSL like here http://drupal.org/node/1466480
10. Try not to use a contributed module just because it is giving a unctionality, if you can take the required code and implement it from your custom module, it will have less load.
11. Try to avoid slow queries
12. Yes, if you can have CDN facility, it will be good as in that case the data will be fetched from the distributed system. If you can have distributed DB privilege, it will be better as in that case the DB & file requests will not be on the same server
Hope it helps.
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