In modifying skills.2da for use with a 4e rules set, I have found great difficulty in removing some skills. I however find no issue with adding new skills. Replacing any skill, especially if you want to rewrite what that skill does, is not suggested. Instead, simply add a new skill. In the case of stealth skills, and skills pertaining to internal perception lists, or of skills related to spellcasting and of identifying those spells as they are cast, I can only say that you should just go with what the engine has. If you want other things, add them separately instead of making a new skill, and if need be, increase the number of skill points given per level to compensate for the new variety.
You'll want to read up on the aspects of the skills.2da, specifically the Untrained column, and the AllClassesCanUse column. You'll need to change the class derived skill lists. To do that, see details about classes.2da, specifically the column SkillsTable. From there, you can track the data to a list of skills and whether or not the skill is a class skill, which relates back to the columns in skills.2da I have mentioned.
http://nwn.wikia.com/wiki/Skills.2da
http://nwn.wikia.com/wiki/Classes.2da
http://nwn.wikia.com...Cls_skill_*.2da
Have you given any thought to how you will apply permanent skill modifiers to characters?