Read a few notches down in this forum -- someone had a bad experience, and there was/is some good discussion about how it happened and why it happened and how to avoid it next time.
A few general suggestions (hopefully others will add/edit/refute):
- Figure out yourself whether you want to start people off in this system with carefully nuanced characters or simple characters painted with broad strokes. I went the broad-strokes route -- pretty much every power my PCs had was at +10, and I gave everyone an offensive power, a defensive power, and a movement power.
- Make the characters yourself. The archetypes are... best for nuanced games. They tend to get plastered by minmaxed characters, though -- and minmaxed is likely what you'll make if you make bad guys yourself.
- Keep things simple. Honestly, do you need to do much work to make people understand how M&M skills work? Not really. Most of my first session was about how powers work and how those new combat rules play -- and my players, who know D&D and d20 Modern inside and out, used the skills they knew by heart and went to town with the powers and combat rules.
- Differentiate D&D strategy and M&M strategy. Taking a hit is not the end of the world. Getting stunned is not the end of the world. Since you most likely only get one attack, the threat of taking a full-round attack from a monster is much lighter. Hero Points are a good way to avoid a bad thing and a GREAT way to make a good thing possible.
- Use the environment. Trading damage feels a lot like D&D, so have bad guys knock buildings and cars onto people -- even if that's just the flavor text for a Super-Strength or Energy Blast attack. My players loved my description of having the Super-Tough character get slammed back into a brick wall hard enough to leave a spiderweb of cracks and a foot-deep impression, only to have the player then have him hop back down, shake off the dust, and say, "That all you got?" (as he made a damage save after soaking most of the damage)
- Make sure to build bad guys that are an appropriate challenge for your heroes, not pushovers or TPK candidates. Don't send a mentalist against an all-physical group. It'll be ugly, and what's worse -- it won't be fun. Bricks have fun fighting bricks. Blasters have fun fighting blasters. Utility players (speedsters, shapeshifters, etc) do well against each other or against non-minmaxed versions of the above. That's fun.