I have c64 running in Mala on my SNES machine and I love it. It is by far one of the trickiest emulators to set up. It is a really long process, but I love C64 too much to give up on it. I recommend having no more than 50 games for c64 if you really want to work over each game to play seamlessly in the way that I did. Here are the barriers I had to work through:
1) load time: No more LOAD"*",8,1 for me. I do not load the disk files from mala. Even in emulators there is load time, and often a lot of crack intros that I don't want to look at. What I had to do is initially load the game, wait until I get to the game's title screen. Save a snapshot file in vice (not a quicksnapshot), and set mala to load the snapshot files instead of the disk files (In Mala, set game file type to ".VSF" instead of any .D64, .t64, etc.) . Make a snapshot file for each game. Then when i start the game in mala, it starts the snapshot file and I am instantly loaded on the main screen of my game.
2) Non-standardized controls. This is the big one. If you remember back in the day, half of the c64 games used control port 2 instead of 1, and most of them also utilized a keyboard. Some games only used keyboard. To work with this, most people simply have a keyboard docked in their cab, and used player 2 when needed. Since I didn't have a keyboard installed on my project, and didn't want to swap controller ports, I used joy2key to make custom controls for each game. For example, a game of Castle Wolfenstein uses the joystick for aim and move, then the keyboard for functions like search, fire, throw grenade, etc. I set up joy2key to translate button 2 to be fire(left arrow), button 3 to be search(space bar), button 4 to be grenade (Q). Then I instructed Mala to set-up that joy2key configuration on that specific game start. I had to create a configuration for almost every game, and had to create a batch file for mala to start each configuration up. It takes time, which is why I say no more than 50 games. Also, the downside to not having a keyboard is there are a some games that you need a ton of keyboard keys, and those games usually are not playable.
3) Disk swapping. Bigger games like Maniac mansion where you used both sides of the disk are a problem. I just didn't bother with disk swap games. You either need to have the ability to access the the menu to swap disk files, or create a hot swap. I don't remember how to do it, but it was basically setting the game boot to load both disks into Vice at once. Then you have a hotkey that flips between the two disk files. Then there are huge games with like 3 or 4 disk files (I want to say some of the last ninja games, TMNT), I don't know if a hot swap can be easily made for those. It might just be best to have a way to manually load in disk files if you want to have multi disk games.