Design is semi-unique in the fact that your CV is not necessarily the best indicator of what you can achieve. Often a single piece of work that speaks to an employer is just as important as what you have written on your CV. Don't get me wrong - we do live in an age where experience is king and queen and this will help any candidate, but a great portfolio will open some doors.
1. Make sure your portfolio is user friendly
Make it easy for a potential employer to view your work and figure out what the work is about. If you have done work to a brief then put a simple few words about it - don't write a full story about what you did and why you did it. Good creative work speaks for itself - if you have to explain to your client or your potential employer about what you have done then you ain't done it right!
2. Make sure your portfolio is targeted
Do not go along to a job with a large Ad Agency and showcase your photography skills - that'll kill your prospects then and there. The same is also true for the agency that you choose to go for a job with. Do some research about them, take some time to see what kind of work they do and clients they have - then make your portfolio reflect this.
3. A little bit of you
Make sure your portfolio also stands out from the crowd and has your unique stamp. Sure there are general rules over what a portfolio should be like - but after seeing 20 black portfolios - a bright pink one with a few frills (if appropriate) might be just enough to catch a potential employers eye.
Ps. Please don't do the pink frilly portfolio and blame me if you don't get a job - it is a metaphor. (google it)