Mods can make the game a lot more choppy. Especially those mods by Xarwarz that alter the skins of whole planets. It all depends on your graphic card, honestly. Generally, graphic cards are lame for just about anything. Don't be fooled that they append "HD" to their name. Google your graphic card and you'll usually be able to ascertain what it's worth. As for compatibility issues... never heard of a one that indeed slows the game (unless you mean that it prevent you from progressing...)