Here is my solution to this, although it comes with some caveats, read below.
For starters, if you need sku or any other attribute to be available in your rules, enable that in
Manage Attributes by going to that attribute and setting
Use for Promo Rule Conditions to yes.
This rule I've shown is a $15 off purchase off $75, which could be easily changed to $100 off $400. The key here is that we're only going to total items that match all of our criteria.
Special Price does not contain . means that if someone has entered a value into the special price field, then it won't count towards the total. This requires you to enter values like 5.00 or 4.00 that contain a decimal point. If you just slap a 5 in there, it won't pick up a zero and this will fail. Also, the special price start and end date won't factor into this, so you'll have to manually add and remove special pricing. It's not a perfect solution, and I haven't cracked the date comparison in promotions...but this does work.
There are also some examples here of restricting the sale to not include certain skus or things in certain categories. Many people keep a sale category on their site, and this is also a good way to restrict the promo. It's easy to maintain one category of sale items, it's good for sales, and behind the scenes you're using it for this restriction too. If possible, maintain that category and you're all set.
This is one area of magento that I'd love to see improved. There are many logical comparisons I'd like to make that we can't yet. Maybe in 2.0, time to give that a try!