Karlsson, along with Bobby Ryan, Kyle Turris, Clarke MacArthur and Jared Cowen are the Senators' future, while names like Daniel Alfredsson and Jason Spezza are now simply a part of the past.
Spezza was traded this past summer to the Dallas Stars after requesting a fresh start, while longtime captain Alfredsson left two years ago to sign with Detroit as a free agent.
The Senators will look to Turris to take over from Spezza as the number-one centre.
Two years ago Turris was handed the responsibility when Spezza was injured and filled in admirably; now the 25-year-old is looking forward to taking on the job full-time.
"It's going to be a challenge and I'm trying to prepare for that, but I definitely feel I'm more ready than I was a couple years ago when I was put into that position," Turris said. "I'm excited about it and it’s going to be lots of fun."
MacArthur will likely line up on Turris' left as the two found instant chemistry last season, while Ryan or Mark Stone could play on the right.
Ryan, who recently signed a seven-year extension, has also been playing on the left side with Mika Zibanejad, who is expected to centre the second line, and newcomer Alex Chiasson, acquired in the Spezza trade, on the right.
Playing on the left side is nothing new for Ryan as he often did while a member of the Anaheim Ducks.
Ryan has made it clear he's looking for an expanded role, and at this point Senators head coach Paul MacLean says the plan is to have Ryan on the power play as well as the penalty kill.
"When you lose a guy like Spezza and he moves on you've got to replace a lot of different things that he brought to the team," Ryan said. "If I can do that in one regard and they ask me to step up my game in certain areas then certainly it’s something that I would like.
"I think it helps you thrive when you know that you're going out for more shifts. Hopefully for me I get a chance to take on those opportunities and then it just keeps you in the game and you can go from there."
While Zibanejad is pencilled in as the second-line centre, there is some doubt as to whether or not he's ready for the additional responsibility.
At times the 21-year-old has played with poise well beyond his years, but he's also struggled and said it's difficult to battle through those tough times.
"I think the details are very important now and to just be able to play," Zibanejad said. "I don't have room to be worried about mistakes, I just have to play and if mistakes happen I just have to be able to recover. The game's going to come as long as I work hard and do what I'm supposed to, but it's the mental side now that has to take another step as well."
The remaining questions up front are how well Milan Michalek and David Legwand will contribute and if Curtis Lazar is ready to play in the NHL.
The 19-year-old is expected to start the season with the Senators, but management has made it clear Lazar will only remain in the NHL if they feel it's beneficial to his development. It's likely the Senators will let him play ten games before making a final decision. The only options available for Lazar are to remain in the NHL or return to the Edmonton Oil Kings of the Western Hockey League.
Michalek signed a three-year extension in the off-season and if he can remain healthy could contribute offensively. The 29-year-old has the potential to score 20 goals, but only if his knees can hold up. Additionally Spezza's absence could have the greatest impact on Michalek as the two played together on a consistent basis.
"It's going to be different and it's going to be more of a hard-working game now then skill so it's going to be different, but we have to get used to it," said Michalek. "I think we'll play a fast game, a hard working game so it’s good for me that's how I play too so it should be good."
The Senators signed Legwand as a veteran presence and are hopeful he can contribute offensively. If Zibanejad struggles Legwand could have the opportunity to move up the depth chart.
Defensively the Senators will once again rely heavily on Karlsson, but they will need him to be much better in his own end.
No one complained about Karlsson's offensive abilities last season as he scored 20 goals and had 54 assists, but on more than one night MacLean was frustrated at his defensive lapses.
It's highly likely Karlsson will be paired with Marc Methot, as long as Methot can recover from a nagging back injury, or Cowen could find himself rounding out the top pairing.
In all likelihood the Senators will start the season with eight defencemen. Cody Ceci is the only one on a two-way contract, but the Senators were impressed with his play last season and it would be a difficult decision to send him to Binghamton in the American Hockey League.
MacLean is a firm believer that you can't have too many defencemen, but a trade is likely. If the Senators can't sign Methot to an extension the Senators would want to move him and get something in return. Patrick Wiercioch is another player often rumoured to be on the move as he has yet to earn a regular spot in the lineup.
Defence has been the focus in training camp due to the struggles the Senators endured last season. The team gave up the second-most shots on goal and allowed the fourth-most goals in the league.
So far MacLean is pleased with the progress.
"We feel that the scoring chances are down, our shots on goal are down so those are all positives that we take out of it," MacLean said. "Not really surprising that our goal scoring has suffered just a little bit, but we're trying to do this as more of a focus so we feel (goal scoring’s) going to come along once we get better defensively."
The Senators have potential strength in goal with Craig Anderson and Robin Lehner, but both will need to be better than last season.
Neither goaltender had great support last season, but at the same time neither stole too many games. Anderson will likely get the start when Ottawa opens its season Thursday in Nashville, but the Senators have made it clear that whoever gives the team a better chance of winning will play.
If training camp is any indication Ottawa's power play will have a new look as MacLean has been experimenting with using four forwards and one defenceman.
Ottawa ranked 14th last season with the man advantage, but without Spezza goals could be harder to come by and as such MacLean is willing to tinker a little.
"There's always a danger that with four forwards a pass could turn into a turnover and quickly turn into a 2-on-1 going the other way," MacLean said. "It's something we wanted to look at, we've done it in the past with some success, but we've also practised with two defencemen on the power plays to give us both looks."