Plenty. Though the basic mechanics of the game remain largely unchanged, the 4th Edition includes a number of rules fixes and revisions; most minor, though there were a couple of substantial changes as well. Here's a quick checklist:

The biggest change from previous editions is probably John Harper's new Magic system, which was rewritten from the bottom-up to make it better-suited to the Talislantan milieu. Though the new system still uses the Action Table, it is much more open-ended and offers several new features that weren't available before. John also re-engineered the mechanics to work as a solely skill-based system, without the need for the now antique level-based system of past editions. This allows players and Gamemasters more latitiude to customize characters and make them more unique than ever before.

On the technical end, you don't have to roll dice for damage anymore. In John's revised Combat system weapons and attacks have a set Damage Rating that can vary according to the Action Table die roll. So you only need two types of dice to play now, a d20 and a d10 (or just a d20, for you math-savvy types).

Talislanta's numerous archetypes received a much-needed going-over from Adam Sonfield. As a result, both Player-Characters and the Non-Player Characters are a lot more colorful than in the past and are much easier to role-play. We’ve also included over fifty new Sample NPCs for Gamamasters to use in their campaigns.

Last but not least was the reorganization of Talislanta's complex and sometimes overwhelming milieu into a more cohesive format. The new Traveler's Guide section handles this admirably, presenting each region of Talislanta along with its cultures, geography, character-types, creatures, flora and fauna in one easy-to-use source. It also marks the return of the wizard Tamerlin, absent from the scene since writing the Chronicles of Talislanta. For the first time since the game's inception, Gamemasters and players finally have a single reference source that covers everything they need to know about Talislanta. And it only took ten years.