Here are some of the changes I like so far (having just finished reading the book, and creating/converting a few characters, but not having played it yet):
1. Although D&D 3E's class templates are much more flexible than previous editions, they're still rather limiting. Blue Rose's roles start with a fairly simple baseline, then give you lots of leeway in choosing feats and skills. You can replicate d20 classes if you want, but you have many more options, too--and without any added complexity. Also, many feats dropped fairly minor prerequisites (such as +1 base attack bonus), so more characters have the opportunity to take them.
2. With role-based Defense bonuses, you don't have to wear 20-50 pounds of armor to have a decent Defense/AC.
3. I've always felt that D&D's magic system (in any edition) was counter-intuitive: the "prepare now, cast later" mechanic; the rigid spell levels and spell slots; and the lack of any sense of logical paths of study (where learning spell A makes spell B easier to learn). Blue Rose's arcana system has a very different feel, which I find refreshing.
4. Magic items are a little too common in d20--and a little too necessary for survival. Blue Rose focuses on rewards other than loot, and activities other than getting that loot.
5. Combat is streamlined, with the more fiddly tactical details removed. (Most d20 players seem to either love or hate threatened areas, attacks of opportunity, counting 5-foot squares for every action, etc.) Fights should (theoretically) go much faster, allowing more time for other interesting stuff.
6. Damage daves make it easier to track wounds than counting every single hit point. I especially like it as an improvement over how raising or lowering Con impacts HP in d20. In Blue Rose, changing Con makes damage saves harder or easier, serving the same purpose as adding or raising HP, but you no longer have to keep track of changes to maximum HP, too. Also, a drop in Con won't kill you outright until your score is completely delibitated.
7. There are many subtler touches as well, where a simple rule either replaces a lengthy passage in d20, or covers something d20 doesn't. Two examples: a simple formula for the difficulty of breaking objects based on their hardness; a library allowing a hero to take 20 on a Knowledge check.
You still won't be able to replace d20 with True20 for a traditional D&D setting without some work. The biggest obstacle is probably the relatively small number of arcana. The selection will be expanded in the Companion, but is unlikely to include all of the effects common to your typical, high-powered, over-the-top D&D game (with teleporting wizards strewing fireballs, lightning bolts, and conjured allies across the battlefield). Settings other than medieval fantasy would, of course, require even more work.