ExactTarget offers some great insight about HTML e-mails and the challenges they can cause! Variables such as which e-mail client, which browser and which software your clients are using can have an impact.
As such this area of technology gets to be a lot thicker and more complicated than one would first suspect.
If you then mix that with all the cool new tricks for tracking opens, subscribes, unsubscribes and marketing statistics as well as the international and national SPAM laws you are stepping into an area that requires its own experts. The experts exist and they are working with Microsoft! Companies like CoreMotives and ExactTarget for instance.
So if advanced marketing is a focus of yours then start at the top of the trees, in the right forest, with the right tools and the right partners and then get into the nitty gritty.