In 4e, attributes are priced more consistently than 3e. DX and IQ are always 20 points to upgrade by 1, and ST and HT are always 10.

4e doesn't have any kind of Random Characters.

In 4e, HP is based on ST and FP is based on HT, not the other way around.

In 4e, psionics is not skill-based and is relatively simpler.

4e doesn't have language skills; instead, languages are separate, and there are four levels (None, Broken, Accented, Native) rather than the full 3d range.

4e Tech Levels are more consolidated and some things are different. As an example, modern day is TL8 (the digital age), rather than TL7.

4e has more damage types than 3e.

Mental disadvantages in 4e use a 'self-control roll' instead of a Will roll.