All 151 Pokemon have been replaced with entirely new creatures, "Star Beast."
All Star Beast can be caught in-game in one playthrough via one means or another. Their locations are usually not the same as their original game equivalents, though.
Dark and Steel type are here.
Ghost, Bug, and Psychic types now work and interact properly.
The game uses Gen 1-3's attack system, so attacks being physical or special is based on typing. This WILL NOT change.

New evolution stones in Liquid Steel, Holy Soul, and Dark Soul.

There are no trade evolutions any more.

If a trainer can be avoided in any capacity (not talked to or interacted with), there is a chance that trainer may have an unusually powerful team. This is meant to provide a challenge to people that aren't paying attention, as well as spice a playthrough up for Gen 1 veterans.

Several trainer classes have either been replaced or had their team gimmicks diversified.

The difficulty of the game on the whole is a bit harder than vanilla Gen 1, although not substantially so.

All of the Gym Leaders, and several other important trainers, have been replaced.

A lot of new dialogue.

Move Changes:
Several irrelevant moves (I.E: Bind, Bubble, Constrict) have been removed and replaced with better moves.

Cut is now Steel type with base 70 power and a 10% chance to paralyze.
Gust is now Flying type.
Wing Attack has base 65 power now.
Hi Jump Kick and Jump Kick are just Jump Kick now, and it has a base power of 70.
Bite is now Dark type and has a 10% chance to flinch.
Submission now has base 150 power but is otherwise unchanged.
Strength is now Fighting type and has a 10% chance to lower enemy speed.
Skull Bash is now Steel type and has base 150 power.
Spike Cannon is now Steel type.
Flash is now Electric Type, has base 60 power, and has a 30% chance to flinch.

New Moves:

Falcon Punch: Flying type Hyper Beam that has base 140 power.
Hurricane: Base 120 power Flying type attack that has a 30% chance to flinch.
Flash Cannon: Base 80 power Steel type move with a 30% chance to lower SPECIAL.
Mach Punch: Fighting type Quick Attack.
Dragon Claw: Base 80 power Dragon type move.
Hyper Voice: Base 90 power Normal type move.
Dragonbreath: Base 60 power Dragon Type move with a 30% chance to paralyze.
Club: Base 65 power Rock type move with a 10% chance to flinch.
Death Drown: Water type Hyper Beam that has base 170 power.
Wood Hammer: Base 120 power Grass type move that does recoil damage.
Time Stop: Psychic type Wrap / Fire Spin / Clamp.
Drill Run: Ground type move that has base 80 power.
Aerial Ace: Flying type move that has base 60 power and NEVER misses.
Ice Hammer: Base 100 power Ice type move that does recoil damage.
Outrage: Dragon type Thrash that has base 90 power and confuses after a minimum of 3 turns.
Crunch: Base 80 power Dark type move with a 30% chance to lower SPECIAL.
Aura Sphere: Fighting type move that has base 70 power and NEVER misses.
PK Fire: Fire type Hyper Beam that has base 150 power.
Brick Break: Base 75 power Fighting type move that has a 10% chance to lower defense.
Poison Fang: Base 50 power Poison type move that has a 30% chance to poison.
Sludge Bomb: Base 90 power Poison type move that has a 30% chance to poison.
Shadow Claw: Base 70 power Ghost type move.
Ominous Wind: Base 60 power Ghost type move that has a 30% chance to flinch.
PK Starstorm: Psychic type Hyper Beam that has base 150 power.
Bug Bite: Base 60 power Bug type move that has a 10% chance to flinch.
Megahorn: Base 120 power Bug type move.
Dark Pulse: Base 80 power Dark type move with a 10% chance to flinch.
Scald: Base 80 power Water type move with a 30% chance to burn.
Metal Claw: Base 50 power Steel type move with a 10% chance to lower defense.