Mixing is the new making.
Creating new genre from a mix of others is a common thing nowadays. Sometimes it gets silly and goes "3D DELUXE FLAPPY CLASH OF NEED COUNTER 2048", but if mixing is used in a right direction - the results would be mostly great.
Do not copy!
Another clone of successful game could be profitable, if done right, but let's be honest - most clones are garbage.
Have a common sense.
There is no need to overfill games with stuff that average player won't be able to get. Set a goal for a player, but don't make it a torture.
Understand what you are working with.
I seriously doubt that nowadays you can fully recreate Skyrim of The Witcher on a mobile device, due to technical limitations. If you want to make a game with a huge world - use 2D or isometric 3D.
Inspirations from the past.
Crossy Road was based on an idea from Atari 2600 game. Dig!