Creating custom enemies and even custom villain groups in Mission Architect is not difficult. However, creating good enemies and groups is harder and it all revolves around you, the writer. Here are a few tips that should help turn your ho hum villains into something you can be proud of!
Start with an Idea
Have a good basic idea of who/what this enemy is and what he/she/it does that makes it memorable. I'm not talking about specific powers or even backgrounds at this point - you are putting a bad guy into a mission for a reason; that reason changes many of the other decisions.
Be Aware of File Size
Remember that custom villains are expensive in terms of mission file size. An entire custom villain group can quickly eat into your budget. Prepare accordingly! If you make a single group that's using too much memory, you can always make smaller sub groups you use can use in different missions. An example of using a real enemy group would be Arachnos, where there are dozens of critters to use. You could make a 'Wolf Spider' sup group, a 'Mu' sub group, a 'Widow' sub group and many more. That way you can use a sub group that helps focus your story and that saves you file size so you can add those custom Allies or Boss(es).
Think about how hard of a mission you want this to be. If you are making a Test to Destruction mission, you are going to want to make different choices than if you are making an 'I want to tell a cool story' mission. Everything from combinations of powersets, to enemy rank to critter difficulty setting change how hard a custom critter can be.
Related to Difficulty, is the target players Notoriety - your hand crafted uber-tough boss becomes a Lieutenant if they player is on the lowest notoriety setting - which is a perfectly valid a choice for them. Remember that players won't always be seeing your creation in exactly the same way you experience it during testing.
Test Your Creation
Before filling out all the Boss strings and background information and hand crafting a lovely costume, pick the powersets, difficulty and AI that you want him to use, and launch into a test map to see how he fights. Iteration and testing can go a long way towards making a memorable encounter. Once he fights the way you want, go back and...
Fill out the boss chat dialog. This is some of the best way to get your story background to all the players on the team, not just the guy who talked to the contact. If you have a fully custom group, be careful not to go overboard with this, though, since it is easy to overwhelm the player with too much text flying up at once.
Back to testing. Make sure all your flags go off when you expect them to! Ranged Attacks
And last, if at all possible, always try to give your critter a ranged attack. There's nothing sadder than an AV who can't attack the hovering Blaster, 20 feet over his head